| Gastric cancer(GC)is one of the most common malignant tumors threatening human health in the world.Drug resistance is the main cause of recurrence and metastasis of gastric cancer.The study of traditional Chinese medicine which can resist drug resistance can provide new treatment options for clinical treatment of gastric cancer.In this study,the effects of Celastrol on the proliferation,apoptosis and drug resistance of SGC7901/DDP cells were detected,so as to explore its role in reversing drug resistance and provide a theoretical basis for its clinical application.Objective:To explore the effect and mechanism of Celastrol on proliferation and drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP.Methods:1.MTT method was used to detect the proliferation of SGC7901 and SGC7901/DDP cells treated with different concentrations of cisplatin(DDP).The expressions of P-gp,MRP1 and BCRP in SGC7901 and SGC7901/DDP cells were detected by Western blot and RT-qPCR.2.SGC7901/DDP cells were treated with different concentrations of Celastrol for 24h,48h and 72h,and the cell viability was detected by MTT;after Celastrol treatment for 24h,the cell proliferation was detected by EdU method,and the apoptosis was detected by Annexin V-FITC/PI double staining.3.SGC7901/DDP cells were treated with different concentrations of Celastrol for 24 h.The expressions of P-gp,MRP1 and BCRP were detected by Western blot and RT-qPCR.The expression levels of mTOR pathway related proteins were detected by Western blot.4.SGC7901/DDP cells were treated with Celastrol combined with DDP for 24h.The expressions of P-gp,MRP1 and BCRP were detected by Western blot and RT-qPCR.Results:1.The drug resistance index(DRI)of SGC7901/DPP cells was 5.64;SGC7901/DDP cells have higher expression levels of P-gp,MRP1 and BCRP than SGC7901 cells(P<0.05).2.Compared with the control group,0.1-6.4μmol/L of Celastrol significantly inhibited the proliferation of SGC7901/DPP cells in a time and concentration dependent manner(P<0.05);Celastrol inhibited the proliferation and induced apoptosis of SGC7901/DPP cells,compared with the control group(P<0.05).3.Celastrol decreased the expression of P-gp,MRP1 and BCRP in SGC7901/DPP cells(P<0.05);Celastrol significantly decreased the expression of mTOR signaling pathway related proteins compared with the control group(P<0.05).4.Celastrol combined with cisplatin reduced the expression of P-gp,MRP1 and BCRP in SGC7901/DPP cells(P<0.05).Conclusion:Celastrol can inhibit the proliferation of the SGC7901/DDP cells,induce their apoptosis,and reduce the expression of P-gp,MRP1 and BCRP,probably by inhibiting the expression of the proteins related to the mTOR signaling pathway. |
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