姜黄素通过ATK/FoxM1信号通路调控胃癌干细胞增殖及凋亡

Curcumin effect on proliferation and apoptosis of gastric cancer stem cells via ATK/FoxM1 signaling pathway

背景:姜黄素对多种肿瘤细胞及肿瘤干细胞有抑制作用,但其对胃癌干细胞的影响及作用机制尚未见报道。目的:探索姜黄素对胃癌干细胞的影响及作用机制。方法:利用肿瘤球形成实验和胃癌表面标记物(EpCAM及CD44)从胃癌SGC7901细胞系中分离胃癌干细胞;MTT实验检测姜黄素对胃癌干细胞增殖的影响;流式细胞仪检测姜黄素对胃癌干细胞凋亡的影响;Western blot检测胃癌干细胞中FoxM 1、p-AKT及AKT的表达;给予PI3K/AKT信号通路阻断剂LY294002干预胃癌干细胞,研究AKT信号通路与Fox M1信号通路的调控关系。结果与结论:(1)成功从胃癌SGC7901细胞系中分离出了EpCAM+/CD44+双阳性胃癌干细胞;(2)姜黄素可以抑制胃癌干细胞的增殖,促进其凋亡,抑制干细胞中FoxM1及p-AKT的表达;(3)PI3K/AKT信号通路阻断剂LY294002能够抑制胃癌细胞中p-AKT及FoxM1的表达;(4)结果提示,姜黄素可以通过阻断ATK/FoxM1信号通路抑制胃癌干细胞增殖并促进其凋亡。

BACKGROUND： Curcumin has crucial inhibitory effects on various cancer cells and cancer stem cells.However, its effect on gastric cancer stem cells and the underlying mechanism of this effect are unclear.OBJECTIVE： To explore the effect of curcumin on gastric cancer stem cells and the underlying mechanism.METHODS： Tumor sphere-forming assay and gastric cancer stem cell markers（EpCAM and CD44） were used to separate gastric cancer stem cells from gastric cancer SGC7901 cell lines. Effects of curcumin on the proliferation and apoptosis of gastric cancer stem cells were determined by MTT and flow cytometry analysis, respectively. Western blot analysis was used to detect the expression levels of FoxM1, p-AKT,and AKT. LY294002, an inhibitor of the PI3K/AKT pathway, was used to determine the regulatory relationship between AKT and FoxM1 signaling pathways.RESULTS AND CONCLUSION： The EpC AM＋/CD44＋ gastric cancer stem cells were successfully isolated from SGC7901 cells. MTT assay showed that curcumin inhibited the proliferation of gastric cancer stem cells, while flow cytometry analysis showed that curcumin induced apoptosis in gastric cancer stem cells.In addition, the expression levels of p-AKT and FoxM1 were decreased by curcumin treatment. After being treated by LY294002, the expression levels of p-AKT and FoxM1 were down-regulated markedly. In conclusion, curcumin can inhibit cell proliferation and induce apoptosis in gastric cancer stem cells via the ATK/FoxM1 signaling pathway.