南方医科大学学报2024,Vol.44Issue(8):1476-1484,9.DOI:10.12122/j.issn.1673-4254.2024.08.06
桑黄酮G通过调控PI3K/AKT/mTOR通路抑制胃癌细胞的生长、迁移和侵袭
Kuwanon G inhibits growth,migration and invasion of gastric cancer cells by regulating the PI3K/AKT/mTOR pathway
摘要
Abstract
Objective To investigate the effects of kuwanon G(KG)on proliferation,apoptosis,migration and invasion of gastric cancer cells and the molecular mechanisms.Methods The effects of KG on proliferation and growth of gastric cancer cells were assessed with CCK-8 assay and cell clone formation assay,by observing tumor formation on the back of nude mice and using immunohistochemical analysis of Ki-67.The effect of KG on cell apoptosis was analyzed using Annexin V-FITC/PI apoptosis detection kit,Western blotting and TUNEL staining.The effects of KG on cell migration and invasion were detected using Transwell migration and invasion assay and Western blotting for matrix metalloproteinase(MMP).The role of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway in KG-mediated regulation of gastric cancer cell proliferation,migration,and invasion was verified by Western blotting and rescue assay.Results KG significantly inhibited proliferation and reduced clone formation ability of gastric cancer cells in a concentration-dependent manner(P<0.05).KG treatment also increased apoptosis,enhanced the expressions of cleaved caspase-3 and Bax,down-regulated Bcl-2,lowered migration and invasion capacities and inhibited the expression of MMP2 and MMP9 in gastric cancer cells(P<0.05).Mechanistic validation showed that KG inhibited the activation of the PI3K/AKT/mTOR pathway,and IGF-1,an activator of the PI3K/AKT/mTOR pathway,reversed the effects of KG on proliferation,migration and invasion of gastric cancer cells(P<0.05).Conclusion KG inhibits proliferation,migration and invasion and promotes apoptosis of gastric cancer cells at least in part by inhibiting the activation of the PI3K/AKT/mTOR pathway.关键词
胃癌/桑黄酮G/恶性行为/PI3K/AKT/mTOR通路Key words
gastric cancer/kuwanon G/malignant behaviors/PI3K/AKT/mTOR pathway引用本文复制引用
耿志军,胡建国,杨晶晶,牛民主,刘馨悦,施金冉,刘亦珂,姚新宇,张雨路,张小凤..桑黄酮G通过调控PI3K/AKT/mTOR通路抑制胃癌细胞的生长、迁移和侵袭[J].南方医科大学学报,2024,44(8):1476-1484,9.基金项目
安徽省高校协同创新项目(GXXT-2020-020) (GXXT-2020-020)
安徽省高等学校自然科研究项目(KJ2020A0563) (KJ2020A0563)
安徽省卫生健康科研项目(AHWJ2022b088) (AHWJ2022b088)