2024 年第 6 期 第 0 卷

替米沙坦通过磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路抑制硬化性胃癌细胞增殖

Telmisartan inhibits the proliferation of scirrhous gastric cancer cells through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

作者：柏希慧1刘诗雨2孙媛媛1

英文作者：Bai Xihui1 Liu Shiyu2 Sun Yuanyuan1

单位：1西安交通大学第一附属医院东院区药学部，西安710089；2陕西省西安市阎良区人民医院药剂科，西安710089

英文单位：1Department of Pharmacy of Eastern District the First Affiliated Hospital of Xi′an Jiaotong University Xi′an 710089 China; 2Department of Pharmacy People′s Hospital of Yanliang District of Xi′an City Shaanxi Province Xi′an 710089 China

关键词：替米沙坦；硬化性胃癌；磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路；增殖

英文关键词：Telmisartan;Scirrhousgastriccancer;Phosphatidylinositol3-kinase/proteinkinaseB/mammaliantargetofrapamycinsignalingpathway;Proliferation

• 摘要：

• 目的 研究替米沙坦对硬化性胃癌（SGC）细胞增殖的影响，并探讨其作用机制。方法 常规培养胃癌细胞MKN1和SGC细胞HSC45。采用细胞计数盒8实验检测替米沙坦对MKN1和HSC45增殖能力的影响；流式细胞仪检测替米沙坦对HSC45凋亡和细胞周期的影响；蛋白质印迹法检测激活替米沙坦对HSC45自噬和磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路相关蛋白表达的影响；采用PI3K/AKT/mTOR信号通路激活剂SC79和替米沙坦共同处理HSC45，分别检测激活PI3K/AKT/mTOR信号通路后，替米沙坦对HSC45增殖、凋亡、自噬和细胞周期的影响。结果 替米沙坦呈浓度和时间依赖性抑制MKN1和HSC45细胞增殖（均P＜0.001），且对HSC45细胞增殖抑制效果更为显著（P＜0.05）。替米沙坦组HSC45早期凋亡率、LC3Ⅱ/Ⅰ蛋白表达量、G0/G1期细胞周期比例均高于对照组［（26.2±2.6）%比（1.3±0.4）%、（1.02±0.09）比（0.29±0.04）、（53.4±3.4）%比（38.1±2.9）%］，磷酸化PI3K、磷酸化AKT和磷酸化mTOR蛋白表达均低于对照组（均P＜0.05）。替米沙坦组和替米沙坦+SC79组HSC45细胞增殖抑制率、细胞凋亡率、LC3Ⅱ/Ⅰ蛋白表达及G0/G1期细胞比例均高于对照组，但替米沙坦+SC79组均低于替米沙坦组（均P＜0.05）。结论 替米沙坦下调PI3K/AKT/mTOR信号通路，促进SGC细胞凋亡、自噬和周期阻滞，进而抑制SGC细胞增殖能力。

• Objective To investigate the inhibitory effect of telmisartan (TEL) on the proliferation of scirrhous gastric cancer (SGC) cells and to explore its mechanism. Methods Routine culture of gastric cancer cells MKN1 and SGC cells HSC45, Cells Count Kit-8 experiment to detect the effect of TEL on the proliferation ability of MKN1 and HSC45 cells. Flow cytometry was used to detect the effects of TEL on apoptosis and cell cycle of HSC45 cells. Western blotting was used to detect the effects of TEL on autophagy and phosphatidylinositol 3-kinase (PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling pathway related protein expression in HSC45 cells. HSC45 cells were treated with the PI3K/AKT/mTOR signaling pathway activator SC79 and TEL. The effects of TEL on HSC45 cell proliferation, apoptosis, autophagy, and cell cycle were detected, respectively, after activating the PI3K/AKT/mTOR signaling pathway. Results TEL inhibited the proliferation ability of MKN1 and HSC45 cells in a concentration and time dependent manner (both P<0.001), and had a significant inhibitory effect on HSC45 cell proliferation (P<0.05). Compared with the control group, apoptosis rat in HSC45 cells, LC3Ⅱ/Ⅰ protein expression cell cycle arrest in G0/G1 phase rate in TEL group were higher ［（26.2±2.6）% vs （1.3±0.4）%, （1.02±0.09） vs （0.29±0.04）, （53.4±3.4）% vs （38.1±2.9）%］, and phosphorylated PI3K, AKT and mTOR expressions in TEL group were lower (all P<0.05). Compared with the control group, proliferation rate, apoptotic rate, LC3Ⅱ/Ⅰ protein expression, and cell cycle arrest in G0/G1 phase rate in TEL group and TEL+SC79 group were higher, while those in the TEL+SC79 group were lower than the TEL group (all P<0.05). Conclusion TEL downregulates the PI3K/AKT/mTOR signaling pathway, and promotes SGC cell apoptosis, autophagy, and cycle arrest, thereby inhibiting SGC cell proliferation ability.