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Effect of curcumin on proliferation,apoptosis,and chemotherapy resistance of gastric cancer cells by regulating the PI3K/AKT/mTOR signaling pathway
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DOI   10.11656/j.issn.1673-9043.2024.08.06
Key Words   curcumin;gastric cancer;phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin signaling pathway;apoptosis;proliferation;chemotherapy resistance
Author NameAffiliation
ZHONG Yun-feng Department of Anorectal, Wuhan Third Hospital, Wuhan, Hubei 430070, China 
XIAO Yujie Department of Anorectal, Wuhan Third Hospital, Wuhan, Hubei 430070, China 
XIA Gan Department of Anorectal, Wuhan Third Hospital, Wuhan, Hubei 430070, China 
YUAN Simin Department of Anorectal, Wuhan Third Hospital, Wuhan, Hubei 430070, China 
Abstract
    [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.

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