雌激素在衣霉素诱导的内质网应激调控胃癌细胞侵袭力中的作用及机制

Involvement of estrogen in gastric cancer cell invasion regulated by tunicamycin induced-endoplasmic reticulum stress

目的:探讨雌激素在衣霉素(tunicamycin,TM)诱导的内质网应激对胃癌细胞侵袭力的影响及机制.方法:以浓度为3μmol/L的TM单独及联合运用浓度为10-9 m o l/L的1 7β-雌二醇(17β-estradiol,E2)处理胃癌SGC7901细胞24h,Transwell侵袭实验检测细胞侵袭能力,并应用Western blot检测pPERK和糖原合成激酶-3β(glycogen synthase kinase-3β,GSK-3β)蛋白Ser9位点的表达.结果:Transwell侵袭实验显示,联合运用TM+E2处理胃癌SGC7901细胞24 h,可明显改善TM所诱导的内质网应激对细胞侵袭性力的影响.Western blot结果显示,相对于对照组,TM处理组pPERK蛋白的表达明显升高,而Ser9-GSK-3β蛋白的表达明显降低.联合运用TM+E2,可明显降低TM所致的pPERK蛋白的表达,升高Ser9-GSK-3β蛋白的表达,差异均有统计学意义(P<0.01).结论:雌激素可通过改善内质网应激,升高GSK-3β的Ser9位点磷酸化,抑制GSK-3β活性,从而明显增强胃癌细胞的侵袭力.

AIM： To investigate the involvement of estrogen in gastric cancer cell invasion regulated by tunicamycin （TM） induced-endoplasmic reticulum stress and to explore the possible mechanism involved. METHODS： TM （3 μmol/L） alone or in combination with 17β-estradiol （E2, 10-9 mol/L） was incubated with SGC7901 cells for 24 h, with the same concentrations of DMSO and alcohol used as vehicle controls. After treatment, the invasion of gastric cancer cells was evaluated by Transwell chamber assays. The expression of phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （pPERK） and phosphorylated glycogen synthase kinase-3β （GSK-3β） at Ser9 were examined by Western blot analysis.RESULTS： TM induced-endoplasmic reticulum stress, which was demonstrated by increased pPERK, decreased the invasion ability of gastric cancer SGC7901 cells and the phosphorylation of GSK-3β at Ser9. However, simultaneous treatment with E2 increased the invasion of gastric cancer cells by counteracting the activating effect of TM on GSK-3β, causing an increase in the phosphorylation of Ser9-GSK-3β.CONCLUSION： Estrogen may counteract endoplasmic reticulum stress-induced activation of GSK-3β and increase the invasion of gastric cancer cells.