1.Effect of Yifei Jianpi Prescription on Lipopolysaccharide-induced Lung Immune Inflammatory Response in Rats Based on STAT1/IRF3 Pathway
Hongjuan YANG ; Yaru YANG ; Yujie YANG ; Zhongbo ZHU ; Quan MA ; Yanlin WU ; Hongmei LI ; Xuhui ZHANG ; Xiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):146-155
ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 (STAT1)/interferon regulatory factor 3 (IRF3) signaling pathway in a pneumonia model induced by lipopolysaccharide (LPS) and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group, and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling, the rats were randomly divided into the model group, dexamethasone group (0.5 mg·kg-1), and Yifei Jianpi prescription high-dose (12 mg·kg-1), medium-dose (6 mg·kg-1), and low-dose (3 mg·kg-1) groups, with 10 rats in each group. Treatment was administered once daily, and the normal control and model groups received the same volume of normal saline. After 14 days, flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and the content of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) in alveolar lavage fluid (BALF). Hematoxylin-eosin (HE) staining was used to observe lung tissue pathology and score the damage. Thymus weight, spleen weight, and wet-to-dry weight ratio (W/D) were recorded. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT1, IRF3, IL-6, and interferon-alpha (IFN-α) in lung tissues, while Western blot was performed to assess the protein expression of STAT1, IRF3, IL-6, and IFN-α. ResultsCompared with the normal control group, the model group showed significantly increased proportion of B lymphocytes in peripheral blood, decreased proportions of NK cells and CD4+/CD8+ (P<0.05, P<0.01), decreased serum levels of IgG and IgA, significantly increased IgM levels (P<0.01), significantly elevated content of TNF-α, IL-6, and IL-8 in BALF, and significantly decreased IL-10 levels (P<0.01). Lung tissue damage was evident, with significant increases in thymus and spleen weights and a higher W/D ratio (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly upregulated (P<0.05,P<0.01). Compared with the model group, the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood, increased proportions of NK cells and CD4+/CD8+ ratios (P<0.05, P<0.01), significantly increased serum levels of IgG and IgA, significantly decreased IgM levels (P<0.05, P<0.01), significantly reduced levels of TNF-α, IL-6, and IL-8 in BALF, and significantly increased IL-10 levels (P<0.01). Lung tissue damage was alleviated, thymus and spleen weights were significantly reduced, and the W/D ratio was markedly decreased (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly downregulated (P<0.05, P<0.01). ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.
2.Textual Research of Key Information of Classic Formula Xieqingwan Based on Ancient and Modern Literature
Yujie CHANG ; Lyuyuan LIANG ; Jialei CAO ; Xinghang LYU ; Wenxi WEI ; Xiaofang WANG ; Huizhen ZHANG ; Sai REN ; Mengqi WANG ; Bingqi WEI ; Bingxiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):226-234
ObjectiveThis paper aims to systematically collect and organize ancient and modern clauses and studies containing Xieqingwan, excavate and analyze the key information of Xieqingwan, and provide a reference for facilitating the development of the classic formula Xieqingwan. MethodsThe composition, dosage, decocting methods, usage, and other key information of Xieqingwan in ancient traditional Chinese medicine books were collected and analyzed by means of literature research and metrological methods. The modern clinical application of Xieqingwan was summarized. ResultsA total of 42 pieces of effective data involving 32 ancient traditional Chinese medicine books were collected. Xieqingwan was first recorded in Xiaoer Yaozheng Zhijue. The drug origin of this formula is basically clear in the ancient traditional Chinese medicine books. The modern drug usage and decocting method were as follows: Angelicae Sinensis Radix, Gentianae Radix et Rhizoma, Chuanxiong Rhizoma, Gardenia seeds, Radix et Rhizoma Rhei, Notopterygii Rhizoma et Radix, and Saposhnikoviae Radix were grounded to fine powder, decocted with honey, and finally formed into pills with the size of a chicken head (1.5 g). It was suggested that half a pill or one pill were taken for one dose with warm Lophatheri decoction and sugar. The indications and clinical application had developed from the recordings in Xiaoer Yaozheng Zhijue and evolved from pediatrics to ophthalmic otolaryngology, neurology, dermatology, digestion, and respiratory diseases. The main pathogenesis of these diseases is heat in the liver meridian and is treated. The effect of Xieqingwan is "clearing away heat and toxicity, removing fire and relaxing the bowels, and dispersing swelling and relieving pain". It is recommended to use the corresponding preparation methods in the 2020 Edition of Pharmacopoeia of the People's Republic of China. Modern clinical studies are centered around the clinical application of Xieqingwan, which is often modified and used in treating Tourette syndrome, herpes, febrile convulsion, sleepwalking, and insomnia. ConclusionThis paper conducts a thorough textual research of the key information of Xieqingwan, induces its historic evolution, and confirms its key information, so as to provide a reference for the future development of Xieqingwan.
3.Mechanism of IGF2BP2 regulation of PPAR-γ/GLUT4 pathway in insulin resistance induced by sodium arsenite exposure in HepG2 cells
Shiqing XU ; Zhida HU ; Qiyao ZHANG ; Siqi ZHAO ; Yujie WANG ; Xiaohui WANG ; Teng MA ; Li WANG
Journal of Environmental and Occupational Medicine 2025;42(4):400-407
Background Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO2 infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO2 solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L−1); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L−1 NaAsO2 for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO2, NaAsO2+pcDNA3.1-IGF2BP2, and NaAsO2+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L−1 insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO2 concentration and cell viability. When the concentration of NaAsO2 was ≥4 μmol·L−1 , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO2 infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L−1 NaAsO2 treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L−1 NaAsO2 and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO2 group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO2 group, the glucose consumption and glycogen levels were increased in the NaAsO2+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.
4.Textual Research and Clinical Application Analysis of Classic Formula Fangji Fulingtang
Xiaoyang TIAN ; Lyuyuan LIANG ; Mengting ZHAO ; Jialei CAO ; Lan LIU ; Keke LIU ; Bingqi WEI ; Yihan LI ; Jing TANG ; Yujie CHANG ; Jingwen LI ; Bingxiang MA ; Weili DANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):270-277
The classic formula Fangji Fulingtang is from ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han dynasty. It is composed of Stephaniae Tetrandrae Radix, Astragali Radix, Cinnamomi Ramulus, Poria, and Glycyrrhizae Radix et Rhizoma, with the effects of reinforcing Qi and invigorating spleen, warming Yang and promoting urination. By a review of ancient medical books, this paper summarizes the composition, original plants, processing, dosage, decocting methods, indications and other key information of Fangji Fulingtang, aiming to provide a literature basis for the research, development, and clinical application of preparations based on this formula. Synonyms of Fangji Fulingtang exist in ancient medical books, while the formula composition in the Synopsis of the Golden Chamber is more widespread and far-reaching. In this formula, Stephaniae Tetrandrae Radix, Astragali Radix, Cinnamomi Ramulus, Poria, and Glycyrrhizae Radix et Rhizoma are the dried root of Stephania tetrandra, the dried root of Astragalus embranaceus var. mongholicus, the dried shoot of Cinnamomum cassia, the dried sclerotium of Poria cocos, and the dried root and rhizome of Glycyrrhiza uralensis, respectively. Fangji Fulingtang is mainly produced into powder, with the dosage and decocting method used in the past dynasties basically following the original formula. Each bag is composed of Stephaniae Tetrandrae Radix 13.80 g, Astragali Radix 13.80 g, Cinnamomi Ramulus 13.80 g, Poria 27.60 g, and Glycyrrhizae Radix et Rhizoma 9.20 g. The raw materials are purified, decocted in water from 1 200 mL to 400 mL, and the decoction should be taken warm, 3 times a day. Fangji Fulingtang was originally designed for treating skin edema, and then it was used to treat impediment in the Qing dynasty. In modern times, it is mostly used to treat musculoskeletal and connective tissue diseases and circulatory system diseases, demonstrating definite effects on various types of edema and heart failure. This paper clarifies the inheritance of Fangji Fulingtang and reveals its key information (attached to the end of this paper), aiming to provide a theoretical basis for the development of preparations based on this formula.
5.Textual Research and Clinical Application Analysis of Classic Formula Fangji Fulingtang
Xiaoyang TIAN ; Lyuyuan LIANG ; Mengting ZHAO ; Jialei CAO ; Lan LIU ; Keke LIU ; Bingqi WEI ; Yihan LI ; Jing TANG ; Yujie CHANG ; Jingwen LI ; Bingxiang MA ; Weili DANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):270-277
The classic formula Fangji Fulingtang is from ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han dynasty. It is composed of Stephaniae Tetrandrae Radix, Astragali Radix, Cinnamomi Ramulus, Poria, and Glycyrrhizae Radix et Rhizoma, with the effects of reinforcing Qi and invigorating spleen, warming Yang and promoting urination. By a review of ancient medical books, this paper summarizes the composition, original plants, processing, dosage, decocting methods, indications and other key information of Fangji Fulingtang, aiming to provide a literature basis for the research, development, and clinical application of preparations based on this formula. Synonyms of Fangji Fulingtang exist in ancient medical books, while the formula composition in the Synopsis of the Golden Chamber is more widespread and far-reaching. In this formula, Stephaniae Tetrandrae Radix, Astragali Radix, Cinnamomi Ramulus, Poria, and Glycyrrhizae Radix et Rhizoma are the dried root of Stephania tetrandra, the dried root of Astragalus embranaceus var. mongholicus, the dried shoot of Cinnamomum cassia, the dried sclerotium of Poria cocos, and the dried root and rhizome of Glycyrrhiza uralensis, respectively. Fangji Fulingtang is mainly produced into powder, with the dosage and decocting method used in the past dynasties basically following the original formula. Each bag is composed of Stephaniae Tetrandrae Radix 13.80 g, Astragali Radix 13.80 g, Cinnamomi Ramulus 13.80 g, Poria 27.60 g, and Glycyrrhizae Radix et Rhizoma 9.20 g. The raw materials are purified, decocted in water from 1 200 mL to 400 mL, and the decoction should be taken warm, 3 times a day. Fangji Fulingtang was originally designed for treating skin edema, and then it was used to treat impediment in the Qing dynasty. In modern times, it is mostly used to treat musculoskeletal and connective tissue diseases and circulatory system diseases, demonstrating definite effects on various types of edema and heart failure. This paper clarifies the inheritance of Fangji Fulingtang and reveals its key information (attached to the end of this paper), aiming to provide a theoretical basis for the development of preparations based on this formula.
6.Key Information Research and Ancient and Modern Application Analysis of Classic Prescription Houpo Sanwutang
Wenli SHI ; Qing TANG ; Huimin CHEN ; Jialei CAO ; Bingqi WEI ; Lan LIU ; Keke LIU ; Yun ZHANG ; Yujie CHANG ; Yihan LI ; Jingwen LI ; Bingxiang MA ; Lvyuan LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):214-221
Houpo Sanwutang, included in the Catalogue of Ancient Classical Prescriptions (Second Batch), was first recorded in the Synopsis of Golden Chamber written by ZHANG Zhongjing from the Eastern Han dynasty and was modified by successive generations of medical experts. A total of 37 pieces of effective data involving 37 ancient Chinese medical books were retrieved from different databases. Through literature mining, statistical analysis, and data processing, combined with modern articles, this study employed bibliometrics to investigate the historical origin, composition, decoction methods, clinical application, and other key information. The results showed that the medicinal origin of Houpo Sanwutang was clearly documented in classic books. Based on the conversion of the measurements from the Han Dynasty, it is recommended that 110.4 g Magnolia Officinalis Cortex, 55.2 g Rhei Radix et Rhizoma, and 72 g Aurantii Fructus Immaturus should be taken. Magnolia Officinalis Cortex and Aurantii Fructus Immaturus should be decocted with 2 400 mL water first, and 1 000 mL should be taken from the decocted liquid. Following this, Rhei Radix et Rhizoma should be added for further decoction, and then 600 mL should be taken from the decocted liquid. A single dose of administration is 200 mL, and the medication can be stopped when patients restore smooth bowel movement. Houpo Sanwutang has the effect of moving Qi, relieving stuffiness and fullness, removing food stagnation, and regulating bowels. It can be used in treating abdominal distending pain, guarding, constipation, and other diseases with the pathogenesis of stagnated heat and stagnated Qi in the stomach. The above results provide reference for the future development and research of Houpo Sanwutang.
7.Interpretation of the clinical practice guidelines for Ketamine in total joint arthroplasty in 2022
Fan WANG ; Huanhuan XU ; Rui MA ; Yujie MA ; Xianjie WAN ; Ke XU ; Peng XU
International Journal of Surgery 2024;51(3):203-206
The American Association of Hip and Knee Surgeons, the American Academy of Orthopaedic Surgeons, and the American Society of Regional Anesthesia and Pain Medicine collaborated to develop an evidence-based study about the safe and effective use of Ketamine in total joint arthroplasty(TJA). Based on the systematic review and Meta-analysis of several studies, the following conclusions are drawn: Ketamine can effectively relieve the postoperative pain of patients; Ketamine can effectively reduce the occurrence of postoperative nausea and vomiting; Ketamine can reduce the use of postoperative opioids; intraoperative use of Ketamine does not increase the incidence of postoperative adverse reactions. The above conclusions are graded according to the strength of evidence support. This article interprets the guidelines to provide reference for addressing the effectiveness and safety of Ketamine use in TJA.
8.Strategy and significance of Chinese medicine combined with medical hydrogel for disease treatment
Yujie BI ; Dujun MA ; Liping PENG ; Ziqiong ZHOU ; Jing ZHAO ; Houjun ZHU ; Qiuhui ZHONG ; Yuxin YANG
Chinese Journal of Tissue Engineering Research 2024;28(3):419-425
BACKGROUND:Medical hydrogels are new functional polymer materials with three-dimensional structural networks and excellent biocompatibility,which have been widely studied in the field of tissue engineering and drug carriers,but the research on the combination of medical hydrogels and Chinese medicine for the treatment of diseases based on tissue engineering is still in the early exploration stage.Therefore,through the analysis of the mechanism of the role of medical hydrogels,the integration of medical hydrogels and Chinese medicine in the research of the joint application of the article,can better provide ideas for scientific researchers,and the joint application of Chinese medicine and medical hydrogels is of great significance. OBJECTIVE:To explore the strategy and significance of Chinese medicine combined with medical hydrogel for disease treatment based on tissue engineering research. METHODS:PubMed and CNKI were used to retrieve articles about the application of Chinese medicine combined with medical hydrogel in tissue engineering from January 2010 to November 2022,with the Chinese and English search terms"hydrogel,traditional Chinese medicine,drug carrier,tissue engineering".After the initial screening of all articles according to the inclusion and exclusion criteria,the 61 articles with high relevance were retained for review. RESULTS AND CONCLUSION:(1)Although the application of Chinese medicine combined with medical hydrogel is involved in intra-articular,intra-tissue organ,soft tissue wounds,tissue engineering,etc.,except for the clinical application of Chinese medicine combined with hydrogel dressing for soft tissue injury,other aspects are still in the experimental stage.(2)The development of Chinese medicine combined with medical hydrogel has great potential and development prospects,but there is a certain difficulty in the manufacture of the gel with high-performance requirements,and it is difficult to master the physical and chemical properties precisely.(3)At present,the comprehensive view of injectable hydrogel with the characteristics of easy to use,its joint use of Chinese medicine can be extended to a wider range,can be used for joint,organ,tissue engineering-related disease treatment.Smart hydrogel has high sensitivity and reversible transformation can also meet the use of the special environment.During the combined use of Chinese medicine,it also needs to understand the mechanism of action of Chinese medicine components.(4)The strategy of combining Chinese medicine with medical hydrogels for disease treatment should start with matching the therapeutic effects of Chinese medicine on organs,tissues and cells combined with appropriate types of medical hydrogels to make up for the shortcomings of traditional Chinese medicine delivery methods and frequent drug delivery.In tissue engineering,hydrogels can be loaded with stem cells after Chinese medicine intervention,or with both Chinese medicine and stem cells for disease treatment.(5)In future research of combined Chinese medicine and medical hydrogel application,we also need to consider:we should ensure that the biological properties of medical hydrogel can be quantified,and grasp the characteristics of hydrogel with different manufacturing processes of different materials to produce the required medical hydrogel that meets the application conditions.In Chinese medicine,we need to comprehensively understand and analyze the therapeutic effects and application mechanisms of known Chinese medicine monomer and Chinese medicine compound extracts,so as to achieve a more perfect combination between Chinese medicine and medical hydrogel under a more clear mechanism.With the continuous improvement of medical science and technology innovation,the medical hydrogel can be innovatively combined with other traditional treatment methods of Chinese medicine,such as acupuncture,massage,cupping and so on,to be used from multiple angles.
9.Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52
Shengyou LI ; Xue GAO ; Yi ZHENG ; Yujie YANG ; Jianbo GAO ; Dan GENG ; Lingli GUO ; Teng MA ; Yiming HAO ; Bin WEI ; Liangliang HUANG ; Yitao WEI ; Bing XIA ; Zhuojing LUO ; Jinghui HUANG
Journal of Pharmaceutical Analysis 2024;14(1):86-99
A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.
10.Mechanisms on radiation resistance induced by an estrogen receptor in breast cancer cells
Tianpeng YANG ; Shinan ZHANG ; Huilin JI ; Linhui ZHU ; Yujie ZHANG ; Jin HUANG ; Yingren WEN ; Shumei MA ; Xiaodong LIU
Chinese Journal of Radiological Medicine and Protection 2024;44(2):88-95
Objective:To explore the effects of estrogen receptor α (ERα) encoded by protein encoding gene ESR1 on the radiation resistance of breast cancer cells and their molecular mechanisms.Methods:The ESR1 overexpression plasmid was transfected into estrogen receptor (ER)-negative breast cancer cells. Then, the shRNA-ESR1 vector was introduced into ER-positive cell to establish models with different phenotype. The ATG5 mRNA level and protein expression levels of LC3B-I, LC3B-II, P62, FIP200, ATG5, ATG7, ATG12, Beclin1, ULK1 were detected using qPCR and Western blot techniques. Cell death was measured using flow cytometry. The radiation sensitivity was determined through the colony formation assay. The mortality of breast cancer cells under the autophagy gene knockdown and overexpression or treated with estrogen receptor inhibitor (TAM) combined with ionizing radiation were detected by trypan blue staining.Results:Under the condition of 8 Gy X-ray irradiation, the knockdown of ESR1 in ER-positive ZR75 breast cancer cells promoted cell death ( t = 3.49, 3.13, P < 0.05), while the overexpression of ESR1 in ER-negative MDA-MB-231 breast cancer cells inhibited cell death ( t = 4.16, 7.48, P < 0.05). Compared to the control group, the treatment with chloroquine increased the number of formed colonies of ESR1 knockdown ZR75 cells ( t = 8.49, P < 0.05), and inhibiting autophagy could reduce the death of ZR75 cells caused by ESR1 silencing. Under the treatment with ionizing radiation, the overexpression of ESR1 in MDA-MB-231 cells promoted protective autophagy, which, however, was reduced after ESR1 knockdown in ZR75 cells. Furthermore, it was observed that the knockdown of ATG5 in ZR75 cells was associated with reduced autophagy and an increase in cell death ( t = 4.19, 6.39, P < 0.05). In contrast, the overexpression of ATG5 in ZR75 cells reversed the increase in cell death caused by ESR1 knockdown ( t = 1.70, 4.65, P < 0.05). After the treatment of ER-positive ZR75 breast cancer cells with TAM, the expressions of ATG5 and ATG12 decreased, suggesting inhibited autophagy and an increase in cell death ( t = 18.70, P < 0.05). Furthermore, these processes were promoted by ionizing radiation ( t = 16.82, P < 0.05). Conclusions:The estrogen receptor encoded by ESR1 promotes protective autophagy of ER-positive breast cancer cells by increasing ATG5, further leading to radiation resistance in ER-positive breast cancer cells. Treatment with tamoxifen combined with ionizing radiation can increase the radiation sensitivity of ER-positive breast cancer cells.

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