1.PX-478 enhances the effect of lung cancer radiotherapy by regulating HIF-1α-mediated glycolysis
Gengqiang YANG ; Yangyang LI ; Qiyang LI ; Shangzu ZHANG ; Yue YANG ; Ting ZHOU ; Liying ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(7):935-941
AIM:To study the efficacy and molecu-lar mechanism of PX-478 in enhancing radiotherapy effect of lung cancer.METHODS:H460,A549 cells were divided into blank group,radiation group and radiation combined PX-478 group.In addition to the blank group,the radiation group and the PX-478 group were given 2Gy X-ray irradiation to estab-lish the radiation model,and the radiation com-bined with the PX-478 group was given 20 μmol/L PX-478 intervention after modeling,and cultured for 24 h.Inverted microscope was used to observe cell growth and cell number,CCK-8 method was used to detect cell viability,cloning was used to ob-serve cell proliferation,flow cytometry was used to detect cell apoptosis,and Western blot was used to detect HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA pro-tein expression.RESULTS:Compared with blank group,the number of H460,A549 cells in radiation group decreased,cell viability and proliferation abil-ity decreased,cell apoptosis rate increased,HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA protein expression increased(P<0.01).Compared with the radiation group,the number of H460,A549 cells in the radia-tion combined PX-478 group was significantly de-creased,the cell viability and proliferation ability were significantly weakened,the apoptosis rate was significantly increased,and the protein expres-sions of HIF-1α,GLUT1,HK2,PFK1,PKM2 and LDHA were significantly decreased(P<0.01).CONCLU-SION:PX-478 can regulate the HIF-1α-mediated gly-colysis in A549,H460 cells after radiation,regulate the energy metabolism,increase the apoptosis of tumor cells,and improve the effect of radiotherapy.
2.Research progress of traditional Chinese medicine intervention in chemotherapy renal injury
Yeyuan LIU ; Yafeng QI ; Maofu ZHANG ; Xinyu LI ; Yanyun SHEN ; Yu LIU ; Shangzu ZHANG ; Yangyang LI ; Liying ZHANG ; Zhiming ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(4):556-569
Renal injury is one of the common ad-verse reactions in the clinical application of chemo-therapy drugs,which is the main reason why the chemotherapy can not be carried out in the whole cycle.The pathological mechanism of chemothera-py-induced renal injury is very complicated,mainly involving oxidative stress,inflammatory response,apoptosis,mitochondrial dysfunction,and regula-tion of transporters,causing pathological damage to renal tubules or glomeruli.At present,there is no specific pharmacological intervention for the treatment of chemotherapy-induced renal injury.As a treasure of traditional Chinese medicine,tradi-tional Chinese medicine has the advantages of overall regulation,multi-targeting,small adverse re-actions and no obvious drug dependence in the prevention and treatment of chemotherapy-in-duced renal injury.In recent years,there have been more and more studies on the intervention of che-motherapy-induced renal injury by multi-compo-nent and multi-directional intervention of active components,extracts and compounds of tradition-al Chinese medicine,and some progress has been made.A large number of studies have shown that the potential mechanisms of traditional Chinese medicine in preventing and treating renal injury in-duced by chemotherapy include inhibiting oxida-tive stress,reducing inflammatory response and in-hibiting apoptosis.Although there are many stud-ies on the mechanism of action of traditional Chi-nese medicine in the treatment of chemotherapy-induced renal injury,there is still a lack of systemat-ic review.Based on this,this paper summarizes the mechanism of renal injury induced by chemothera-py and the intervention of traditional Chinese medi-cine,so as to provide theoretical support for its clinical treatment and new drug innovation.
3.Research progress of traditional Chinese medicine intervention in chemotherapy renal injury
Yeyuan LIU ; Yafeng QI ; Maofu ZHANG ; Xinyu LI ; Yanyun SHEN ; Yu LIU ; Shangzu ZHANG ; Yangyang LI ; Liying ZHANG ; Zhiming ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(4):556-569
Renal injury is one of the common ad-verse reactions in the clinical application of chemo-therapy drugs,which is the main reason why the chemotherapy can not be carried out in the whole cycle.The pathological mechanism of chemothera-py-induced renal injury is very complicated,mainly involving oxidative stress,inflammatory response,apoptosis,mitochondrial dysfunction,and regula-tion of transporters,causing pathological damage to renal tubules or glomeruli.At present,there is no specific pharmacological intervention for the treatment of chemotherapy-induced renal injury.As a treasure of traditional Chinese medicine,tradi-tional Chinese medicine has the advantages of overall regulation,multi-targeting,small adverse re-actions and no obvious drug dependence in the prevention and treatment of chemotherapy-in-duced renal injury.In recent years,there have been more and more studies on the intervention of che-motherapy-induced renal injury by multi-compo-nent and multi-directional intervention of active components,extracts and compounds of tradition-al Chinese medicine,and some progress has been made.A large number of studies have shown that the potential mechanisms of traditional Chinese medicine in preventing and treating renal injury in-duced by chemotherapy include inhibiting oxida-tive stress,reducing inflammatory response and in-hibiting apoptosis.Although there are many stud-ies on the mechanism of action of traditional Chi-nese medicine in the treatment of chemotherapy-induced renal injury,there is still a lack of systemat-ic review.Based on this,this paper summarizes the mechanism of renal injury induced by chemothera-py and the intervention of traditional Chinese medi-cine,so as to provide theoretical support for its clinical treatment and new drug innovation.
4.PX-478 enhances the effect of lung cancer radiotherapy by regulating HIF-1α-mediated glycolysis
Gengqiang YANG ; Yangyang LI ; Qiyang LI ; Shangzu ZHANG ; Yue YANG ; Ting ZHOU ; Liying ZHANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(7):935-941
AIM:To study the efficacy and molecu-lar mechanism of PX-478 in enhancing radiotherapy effect of lung cancer.METHODS:H460,A549 cells were divided into blank group,radiation group and radiation combined PX-478 group.In addition to the blank group,the radiation group and the PX-478 group were given 2Gy X-ray irradiation to estab-lish the radiation model,and the radiation com-bined with the PX-478 group was given 20 μmol/L PX-478 intervention after modeling,and cultured for 24 h.Inverted microscope was used to observe cell growth and cell number,CCK-8 method was used to detect cell viability,cloning was used to ob-serve cell proliferation,flow cytometry was used to detect cell apoptosis,and Western blot was used to detect HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA pro-tein expression.RESULTS:Compared with blank group,the number of H460,A549 cells in radiation group decreased,cell viability and proliferation abil-ity decreased,cell apoptosis rate increased,HIF-1α,GLUT1,HK2,PFK1,PKM2,LDHA protein expression increased(P<0.01).Compared with the radiation group,the number of H460,A549 cells in the radia-tion combined PX-478 group was significantly de-creased,the cell viability and proliferation ability were significantly weakened,the apoptosis rate was significantly increased,and the protein expres-sions of HIF-1α,GLUT1,HK2,PFK1,PKM2 and LDHA were significantly decreased(P<0.01).CONCLU-SION:PX-478 can regulate the HIF-1α-mediated gly-colysis in A549,H460 cells after radiation,regulate the energy metabolism,increase the apoptosis of tumor cells,and improve the effect of radiotherapy.
5.Progress in the Regulation of Aquaporin-2 by Traditional Chinese Medicine for the Prevention and Treatment of Diabetic Nephropathy
Pu ZHANG ; Shangzu ZHANG ; Xiangdong ZHU ; Lihong TANG ; Yongqiang DUAN ; Min BAI ; Yunhui ZHAO ; Jianqing LIANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(11):2921-2927
Diabetic kidney disease(DKD)is one of the major complications of diabetes mellitus(DM),which significantly affects the survival and quality of life of DM patients.Currently,existing first-line treatment approaches for DKD are ineffective in effectively preventing the occurrence and progression of DKD.Traditional Chinese medicine(TCM)has the advantages of"ultiple pathways,multiple targets,and multiple mechanisms"in treating DKD,and has a broad prospect in the treatment of DKD.Aquaporin-2(AQP2)is a membrane channel protein widely expressed in the kidneys,and its physiological function is highly similar to the function of kidney filtration and reabsorption.Studies have found that various effective components and related formulae of Chinese medicine can improve symptoms in DKD patients by inhibiting the abnormal expression of AQP2.This article provides a review on the role of AQP2 in DKD and the research progress of TCM intervention,aiming to provide insights and references for the development of drugs related to the prevention and treatment of DKD.
6.Multidimensional screening of Astragalus membranaceus small molecules to mitigate carbon ion radiation-induced bystander effects
Zhang LIYING ; Zhang YIMING ; Li YANGYANG ; Li QIYANG ; Zhang SHANGZU ; Miao ZHIMING ; He JINPENG ; Zhou TING ; Yang GENGQIANG ; Wang XIN ; Wang JUFANG ; Liu YONGQI
Journal of Pharmaceutical Analysis 2024;14(10):1531-1534
Existing studies have shown that Astragalus membranaceus(AM)and its active ingredients astragalus polysaccharides,oninon,and astragalus methyl glycosides can attenuate X-ray radiation-induced injury.However,there are no studies on how isoliquiritigenin(ISL)attenuate the bystander effect of bone marrow mesenchymal stem cells(BMSCs)induced by carbon ion radiation therapy for lung cancer.This study aimed to investigate the AM-derived small molecule ISL to enhance radiotherapy sensitivity by attenuating the carbon ion radiation-induced bystander effect(RIBE)in BMSCs to elucidate its mecha-nism of action.In this study,we established a C57BL/6 mouse lung cancer transplantation tumor model in vivo and a co-culture model of A549 cells and BMSCs in vitro,and the models were successfully treated with carbon ions.In further work,we used flow cytometry,immunofluorescence,Western blot,enzyme-linked immunosorbent assay(ELISA),inhibitor,short hairpin RNA(shRNA),Cell Counting Kit-8(CCK-8),and other methods to illustrate the mechanism.In the next experiments,we found that ISL combined with carbon ion radiotherapy had a significant anti-tumor effect and protected BMSCs from radiation damage.The aim of this study was to investigate the potential of ISL in enhancing the sensitivity of lung cancer cells to radiotherapy and attenuating RIBE in both in vitro and in vivo settings.Traditional Chinese medicine combined with radiation therapy is a promising and innovative treatment for non-small cell lung cancer.These results establish a theoretical foundation for further clinical development of ISL as a potential radiosensitizer option.
7.Progress in the Regulation of Aquaporin-2 by Traditional Chinese Medicine for the Prevention and Treatment of Diabetic Nephropathy
Pu ZHANG ; Shangzu ZHANG ; Xiangdong ZHU ; Lihong TANG ; Yongqiang DUAN ; Min BAI ; Yunhui ZHAO ; Jianqing LIANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(11):2921-2927
Diabetic kidney disease(DKD)is one of the major complications of diabetes mellitus(DM),which significantly affects the survival and quality of life of DM patients.Currently,existing first-line treatment approaches for DKD are ineffective in effectively preventing the occurrence and progression of DKD.Traditional Chinese medicine(TCM)has the advantages of"ultiple pathways,multiple targets,and multiple mechanisms"in treating DKD,and has a broad prospect in the treatment of DKD.Aquaporin-2(AQP2)is a membrane channel protein widely expressed in the kidneys,and its physiological function is highly similar to the function of kidney filtration and reabsorption.Studies have found that various effective components and related formulae of Chinese medicine can improve symptoms in DKD patients by inhibiting the abnormal expression of AQP2.This article provides a review on the role of AQP2 in DKD and the research progress of TCM intervention,aiming to provide insights and references for the development of drugs related to the prevention and treatment of DKD.

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