Effect of curcumin on proliferation,apoptosis,and chemotherapy resistance of gastric cancer cells by regulating the PI3K/AKT/mTOR signaling pathway
[Objective]To investigate the effect of curcumin(Cur)on the proliferation,apoptosis,and chemotherapy resistance of gastric cancer cells by regulating the phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling pathway.[Methods]MGC-803 cells were separated into control group,Cur low-dose group,Cur medium dose group,Cur high-dose group,and Cur high-dose+740Y-P group for the detection of MGC-803 cell proliferation and apoptosis behavior.MGC-803/DDP cells were separated into blank group,Cur group,cisplatin(DDP)group,Cur+DDP group,and Cur+DDP+740Y-P group for the detection of chemotherapy resistance in MGC-803/DDP cells.Cloning experiments and CCK-8 were applied to detect MGC-803 or MGC-803/DDP cell proliferation;flow cytometry was applied to detect apoptosis of MGC-803 or MGC-803/DDP cells;Western blot was applied to detect the expression of anti-proliferating cell nuclear antigen(PCNA),Bcl2 associated X protein(Bax),multidrug resistance associated protein 1(MRP1),p-PI3K,p-AKT,and p-mTOR proteins in cells.[Results]Compared with the control group,the colony formation rate,proliferative ability,and expression of PCNA,p-PI3K,p-AKT,and p-mTOR proteins in MGC-803 cells reduced in the Cur low-dose group,Cur medium dose group,and Cur high-dose group,the apoptosis rate and the expression of Bax protein increased,in a dose-dependent manner(P<0.05),the results indicated that Cur could inhibit PI3K/AKT/mTOR pathway and MGC-803 cell proliferation,and induce cell apoptosis;compared with the Cur high-dose group,the colony formation rate,proliferative ability,and expression of PCNA,p-PI3K,p-AKT,and p-mTOR proteins in MGC-803 cells increased in the Cur high-dose+740Y-P group,the apoptosis rate and expression of Bax protein decreased(P<0.05),these results indicated that Cur could inhibit the proliferation of MGC-803 cells and induce apoptosis by inhibiting PI3K/AKT/mTOR pathway.Compared with the blank group,the colony formation rate,proliferative ability,and expression of PCNA,p-PI3K,p-AKT,and p-mTOR proteins in MGC-803 cells in the Cur and DDP groups reduced,the apoptosis rate increased(P<0.05),the results showed that MGC-803/DDP cells had higher drug resistance and PI3K/AKT/mTOR pathway activation than MGC-803 cells;compared with the Cur and DDP groups,the colony formation rate,proliferative ability,and expression of PCNA,p-PI3K,p-AKT,and p-mTOR proteins in MGC-803 cells in the Cur+DDP group decreased,the apoptosis rate increased(P<0.05),the results indicated that Cur could inhibit PI3K/AKT/mTOR pathway and reduce drug resistance of MGC-803/DDP cells;compared with the Cur+DDP group,the colony formation rate,proliferative ability,and expression of PCNA,p-PI3K,p-AKT,and p-mTOR proteins in MGC-803 cells in the Cur+DDP+740Y-P group increased,the apoptosis rate decreased(P<0.05),these results indicated that Cur might decrease the drug resistance of MGC-803/DDP cells by inhibiting PI3K/AKT/mTOR pathway.[Conclusion]The mechanism of Cur inhibiting MGC-803 cell proliferation,promoting cell apoptosis and reducing DDP resistance may be related to inhibition of PI3K/AKT/mTOR pathway.