1.Isorhamnetin mediates CYP1B1/NF-κB signaling to inhibit breast cancer progression and enhance paclitaxel sensitivity
Dongwei FAN ; Benxin CHEN ; Yousheng YU ; Congwen JIN ; Cheng HUANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(5):842-851
Objective To explore the biological mechanisms of isorhamnetin(ISO)inhibition of breast cancer(BC)progression and effects on paclitaxel sensitivity by in vivo and in vitro experiments.Methods The effects of ISO on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.ISO biological functions were analyzed and core target genes were identified by genome-wide microarrays,functional enrichment and protein-protein interactions(PPI).CYP1B1 expression characterization and prognosis in BC were assessed by quantitative Real-time polymerase chain reaction(qRT-PCR),Western blotting(WB),and Kaplan-Meier plotter database.The effects of CYP1B1 overexpression on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.The effects of ISO and CYP1B1 on BC tumor growth were analyzed by establishing a subcutaneous graft tumor animal model and verified by histological analysis with immunohistochemistry(IHC)and hematoxylin and eosin(HE)staining.The effects of ISO and CYP1B1 on NF-κB signaling were analyzed by qRT-PCR and WB.The effect of ISO combined with paclitaxel on BC progression was analyzed by in vitro and in vivo experiments.Results The results of CCK-8 assay showed that ISO inhibited the viability of MDA-MB-231 cells with an IC50 value of 11.93 μmol/L;the scratch,Transwell invasion and apoptosis assays confirmed that ISO inhibited the migration and invasion of MDA-MB-231 cells and promoted apoptosis(P<0.05).Volcano plot showed a total of 80 differentially expressed genes(DEGs),of which ISO promoted the expression of 27 genes and inhibited the expression of 53 genes.Gene set enrichment analyses showed that DEGs were mainly enriched in the signaling of organic hydroxyl compound metabolic process,inflammatory response,sterol metabolic process,and nuclear factor-κB(NF-κB).qRT-PCR,WB,and Kaplan-Meier plotter results showed that CYP1B1 mRNA and protein expression was increased in BC and mediated worse prognosis(P<0.05).CCK-8,scratch,Transwell invasion and apoptosis assays showed that CYP1B1 overexpression enhanced MDA-MB-231 cell viability,migration and invasion,and inhibited apoptosis,which was reversed by the addition of ISO(P<0.05).The results of in vivo experiments showed that ISO downregulated CYP1B1 expression and attenuated NF-κB signaling(P<0.05).The results of in vitro and in vivo experiments showed that ISO combined with paclitaxel significantly inhibited BC cell viability and tumor growth(P<0.05).Conclusion ISO inhibits BC malignant biological behavior by modulating the CYP1B1/NF-κB signaling axis,and ISO enhances paclitaxel sensitivity.
2.Isorhamnetin mediates CYP1B1/NF-κB signaling to inhibit breast cancer progression and enhance paclitaxel sensitivity
Dongwei FAN ; Benxin CHEN ; Yousheng YU ; Congwen JIN ; Cheng HUANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(5):842-851
Objective To explore the biological mechanisms of isorhamnetin(ISO)inhibition of breast cancer(BC)progression and effects on paclitaxel sensitivity by in vivo and in vitro experiments.Methods The effects of ISO on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.ISO biological functions were analyzed and core target genes were identified by genome-wide microarrays,functional enrichment and protein-protein interactions(PPI).CYP1B1 expression characterization and prognosis in BC were assessed by quantitative Real-time polymerase chain reaction(qRT-PCR),Western blotting(WB),and Kaplan-Meier plotter database.The effects of CYP1B1 overexpression on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.The effects of ISO and CYP1B1 on BC tumor growth were analyzed by establishing a subcutaneous graft tumor animal model and verified by histological analysis with immunohistochemistry(IHC)and hematoxylin and eosin(HE)staining.The effects of ISO and CYP1B1 on NF-κB signaling were analyzed by qRT-PCR and WB.The effect of ISO combined with paclitaxel on BC progression was analyzed by in vitro and in vivo experiments.Results The results of CCK-8 assay showed that ISO inhibited the viability of MDA-MB-231 cells with an IC50 value of 11.93 μmol/L;the scratch,Transwell invasion and apoptosis assays confirmed that ISO inhibited the migration and invasion of MDA-MB-231 cells and promoted apoptosis(P<0.05).Volcano plot showed a total of 80 differentially expressed genes(DEGs),of which ISO promoted the expression of 27 genes and inhibited the expression of 53 genes.Gene set enrichment analyses showed that DEGs were mainly enriched in the signaling of organic hydroxyl compound metabolic process,inflammatory response,sterol metabolic process,and nuclear factor-κB(NF-κB).qRT-PCR,WB,and Kaplan-Meier plotter results showed that CYP1B1 mRNA and protein expression was increased in BC and mediated worse prognosis(P<0.05).CCK-8,scratch,Transwell invasion and apoptosis assays showed that CYP1B1 overexpression enhanced MDA-MB-231 cell viability,migration and invasion,and inhibited apoptosis,which was reversed by the addition of ISO(P<0.05).The results of in vivo experiments showed that ISO downregulated CYP1B1 expression and attenuated NF-κB signaling(P<0.05).The results of in vitro and in vivo experiments showed that ISO combined with paclitaxel significantly inhibited BC cell viability and tumor growth(P<0.05).Conclusion ISO inhibits BC malignant biological behavior by modulating the CYP1B1/NF-κB signaling axis,and ISO enhances paclitaxel sensitivity.
3.The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes.
Yanlin LUO ; Yibing CHEN ; Huan JIN ; Benxin HOU ; Hongsheng LI ; Xiang LI ; Lingfeng LIU ; Yuan ZHOU ; Yonghua LI ; Yong Sang SONG ; Quentin LIU ; Zhengzhi ZOU
Acta Pharmaceutica Sinica B 2023;13(6):2645-2662
Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types. Tumor-associated macrophages (TAMs) play a key role in promoting tumor malignant progression and therapy resistance. However, the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic. This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo. TAMs have been found to suppress cervical cancer cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells. In cancer cells, miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis. Moreover, the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, in clinical cervical cancer cases, ALOX15 is negatively associated with macrophages infiltration, which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer. Moreover, both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer. Altogether, this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.
4.Effect of RORγ gene on proliferation and migration of colon cancer cells
Changyi Fang ; Xiaofei Pan ; Changjun Yu ; Ping Wu ; Benxin Chen ; Bao Li ; Gan Zhang ; Yuyong Gong ; Yang Li
Acta Universitatis Medicinalis Anhui 2023;58(4):603-608
Objective:
To investigate the effects of retinoid-related orphan receptor γ (RORγ) gene on proliferation and metastasis of human colon cancer cells.
Methods:
RORγ knockdown cell lines were constructed and the knockdown efficiency was detected by RT-qPCR and Western blot assays ; MTT,colony formation,Transwell and wound healing assays were used to detect cell proliferation and metastasis ; the expression of epithelial-mesenchymal transition (EMT) related proteins was detected by Western blot.The relationship between RORγ gene expression and immune cell infiltration in tumor microenvironment was analyzed using TIMER 2. 0 database.
Results :
The knockdown of RORγ enhanced the viability (F = 157. 40,P<0. 01) ,clonogenesis (F = 61. 35,P<0. 01) ,migration (F = 13. 00,P<0. 01) ,invasion (F = 21. 26,P<0. 01) and wound healing ability (F = 877. 2,P<0. 01) of colon cancer cells,inhibited the expression of E-Cadherin,and promoted the expression of vimentin and N-Cadherin.TIMER 2. 0 database analysis showed that RORγ expression in colon adenocarcinoma ( COAD) tissues was associated with multiple immune cell infiltrates.
Conclusion
Downregulation of RORγ expression promoted the proliferation and metastasis of colon cancer cells.
5.Application of ultrasound-guided stellate ganglion block after operation in perioperative period of thyroid cancer patients
Xiaoming LI ; Min ZHOU ; Jun SHEN ; Benxin CHEN
Chinese Journal of Postgraduates of Medicine 2020;43(9):784-788
Objective:To explore the application value of ultrasound-guided stellate ganglion block in perioperative period of thyroid cancer patients.Methods:From March 2018 to November 2019, in the Second People′s Hospital of Lu′an, Anhui Province, the clinical data of 80 thyroid cancer patients who had underwent open radical operation were retrospectively analyzed. Among them, ultrasound-guided stellate ganglion block was performed in 40 cases (observation group), while ultrasound-guided stellate ganglion block was not performed in 40 cases (control group). The pain digital score (NRS) 6, 12 and 24 h after operation was evaluated. The levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) 24 h after operation were detected. The indexes of cellular immune function (CD 4+, CD 8+ and CD 4+/CD 8+) 24 h after operation, serum parathyroid hormone (PTH) before operation and 48 h after operation were detected. The postoperative complication was observed. Results:The NRS 6, 12 and 24 h after operation in observation group were significantly lower than that in control group: (3.6 ± 0.3) scores vs. (4.3 ± 0.4) scores, (2.1 ± 0.2) scores vs. (3.5 ± 0.3) scores and (2.6 ± 0.2) scores vs. (3.6 ± 0.3) scores, and there was statistical difference ( P<0.01). The TNF-α, hs-CRP and IL-6 24 h after operation in observation group were significantly lower than those in control group: (85.9 ± 6.8) μg/L vs. (263.5 ± 13.7) μg/L, (6.1 ± 1.6) mg/L vs. (12.3 ± 2.5) mg/L and (236.9 ± 8.6) μg/L vs. (388.9 ± 15.5) μg/L, the CD 4+, CD 8+ and CD 4+/CD 8+ were significantly higher than those in control group: 0.036 ± 0.013 vs. 0.024 ± 0.010, 0.034 ± 0.013 vs. 0.026 ± 0.009 and 1.9 ± 0.1 vs. 1.4 ± 0.1, and there were statistical differences ( P<0.01). There was no statistical difference in PTH before operation between 2 groups ( P>0.05); the PTH 48 h after operation in observation group was significantly higher than that in control group: (29.8 ± 3.9) μg/L vs. (18.7 ± 2.0) μg/L, and there was statistical difference ( P<0.01). The incidence of postoperative complication in observation group was significantly lower than those in control group: 5.0% (2/40) vs. 25.0% (10/40), and there was statistical difference ( χ2 = 4.804, P<0.05). Conclusions:Ultrasound-guided right stellate ganglion block can effectively relieve postoperative pain, reduce inflammatory reaction, improve immunity, promote the recovery of parathyroid function, and reduce the incidence of postoperative complication in patients with thyroid cancer.
6. Analysis of bowel cleansing situation and influencing factors in patients before colonoscopy
Shaolian XU ; Tang TANG ; Jing CHEN ; Yousheng YU ; Zhenxiang ZHU ; Benxin CHEN
Chinese Journal of Practical Nursing 2019;35(29):2256-2262
Objective:
To investigate the situation and influencing factors of bowel cleansing in patients before colonoscopy, and to provide reference for guiding patients′ bowel preparation.
Methods:
The clinical data of 421 patients undergoing electronic colonoscopy in the endoscopy center of the second people′s hospital of Lu′an city in Anhui Province from April to September 2018, Prospective collection by systematic sampling, including general data of patients, clinical data of bowel preparation and score of Boston bowel preparation scale. Univariate analysis and logistic regression analysis were performed on the relevant factors of bowel preparation.
Results:
Among the 421 patients, 52 cases were not eligible for intestinal cleaning, and the unqualified rate was 12.35%(52/421). Logistic regression analysis showed that: Total amount of drinking water prepared for intestinal tract before colonoscopy (
7.Male sexual function after laparosco-pic and laparotomye section in patients with lower rectal cancer
Cheng HUANG ; Yongxiang LI ; Benxin CHEN
The Journal of Practical Medicine 2015;31(14):2291-2294
Objective To investigate the effects of laparoscopic and open resection with pelvic autonomic nerve preservation (PANP) on sexual function of male patients with lower rectal cancer. Methods Total 177 male patients with lower rectal cancer received surgery from September 2008 to December 2013 were enrolled into two groups: the laparoscopic PANP group (n = 105) and the open PANP group (n = 72). The classifications of erectile and ejaculatory functions were used to evaluate the sexual functions of patients at 6 months and 12 months post-operation, respectively. The effect of different operation on the sexual function of the male patients was compared between the two groups. Results The incidence rates of erectile dysfunction at 6 months and 12 months post-operation in the laparoscopic group were lower than those in the laparotomy group (P < 0.05). The incidence rates of ejaculatory dysfunction at 6 months and 12 months post-operation in the laparoscopic group were also lower than those in the laparotomy group (P < 0.05). Conclusion The laparoscopic resection with PANP in patients with lower rectal cancer can not only clearly reveal pelvic autonomic nerve and effectively protect them, but also reduce the incidence of postoperative sexual dysfunction.
8.Efficacy of sorafenib combined with capecitabine in Hui versus Han residents with advanced hepatocellular carcinoma in Sanya, Hainan, China: a comparative analysis
Long CHEN ; Dong LIANG ; Benxin HOU
Journal of Clinical Hepatology 2015;31(6):895-
ObjectiveTo compare the clinical efficacy of sorafenib combined with capecitabine in Hui versus Han residents with advanced hepatocellular carcinoma (HCC) in Sanya, Hainan, China. MethodsA total of 96 Hui and Han residents with advanced HCC took oral capecitabine 1500 mg/m2 twice daily for 14 days followed by a 7-day withdrawal, which was repeated at least twice; besides, sorafenib was given orally at a dose of 400 mg twice daily until tumor progression occurred. Comparison of continuous data between the two groups was made by t test, while comparison of categorical data was made by chi-square test. ResultsIn the two groups of Hui and Han patients, the rates of alpha-fetoprotein reduction were 60.9% and 40.0%, respectively (χ2=4.173, P=0.041); the rates of serum ferritin reduction were 50.0% and 30.0%, respectively (χ2=4.007, P=0.027); the rates of tumor regression were 54.3% and 34.0% as shown by CT (χ2=4.030, P=0.045); the response rates were 32.6% and 14.0%, respectively (χ2=4.697, P=0.030). Survival analysis suggested the combination of sorafenib and capecitabine had provided a significantly higher overall survival rate in Hui patients than in Han patients (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). ConclusionIn Sanya, a combination of sorafenib and capecitabine has better efficacy in Hui patients with advanced HCC than in Han patients, and the former have a higher overall survival rate.


Result Analysis
Print
Save
E-mail