目的：探讨银杏内酯B（GKB）是否通过阻抑PI3K/Akt/mTOR信号通路抑制胃癌HGC-27细胞的增殖、凋亡、迁移及侵袭。方法：将HGC-27细胞分为对照、GKB低剂量（100 mg/L）、GKB高剂量（200 mg/L）、GKB高剂量（200 mg/L）+740Y-P（PI3K激活剂）、Ly294002（PI3K抑制剂）组。采用MTT、Edu、FCM、Transwell实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，qPCR和WB法分别检测各组细胞中PI3K mRNA、Akt mRNA、mTOR mRNA和Ki-67、caspase-3、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR蛋白的表达。构建胃癌HGC-27细胞裸鼠移植瘤模型，观察GKB对移植瘤生长的影响，WB法检测移植瘤组织中Ki-67、caspase-3、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR蛋白的表达。结果：体外实验结果表明，与对照组相比，GKB低剂量组、GKB高剂量组、Ly294002组HGC-27细胞的增殖活力及细胞增殖率、迁移和侵袭细胞数，PI3K、Akt、mTOR mRNA表达，以及Ki-67、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR蛋白表达均显著降低（均P<0.05）；细胞凋亡率、caspase-3蛋白表达均显著升高（均P<0.05）；740Y-P可部分逆转GKB对HGC-27细胞的抑制作用（均P<0.05）。荷瘤裸鼠实验结果显示，GKB可显著抑制HGC-27细胞裸鼠移植瘤的生长（P<0.05），且可下调PI3K/Akt/mTOR通路相关蛋白的表达。结论：GKB可通过阻抑PI3K/Akt/mTOR信号通路而抑制胃癌HGC-27细胞增殖、迁移与侵袭并促进其凋亡。

Objective: To investigate whether ginkgolide B (GKB) inhibits the proliferation, apoptosis, migration and invasion of gastric cancer HGC-27 cells by blocking the PI3K/Akt/mTOR signaling pathway. Methods: Gastric cancer HGC-27 cells were divided into control group, low-dose GKB (100 mg/L) group, high-dose GKB (200 mg/L) group, high-dose GKB (200 mg/L)+740Y-P (PI3K activator) group, and Ly294002 (PI3K inhibitor) group. MTT and Edu, FCM, Transwell tests were used to detect the proliferation, apoptosis, migration and invasion abilities of HGC-27 cells in each group. The expressions of PI3K mRNA, Akt mRNA, mTOR mRNA, and the protein expressions of Ki-67, caspase-3, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in cells of each group were detected by qPCR and Western blotting. A nude mouse transplanted tumor model of gastric cancer HGC-27 cells was established. The effect of GKB on the growth of transplanted tumors was observed. Wesern blotting was used to detect the protein expressions of Ki-67, caspase-3, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in transplanted tumor tissues. Results: The results of in vitro experiments indicated that, compared with the control group, the proliferative activity, cell proliferation rate, the numbers of cell migration and invasion, the expression levels of PI3K mRNA, Akt mRNA and mTOR mRNA, and the protein expression levels of Ki-67, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR of HGC-27 cells in low-dose GKB group, high-dose GKB group and Ly294002 group, reduced significantly (all P<0.05). The apoptosis rate and the expression of caspase-3 protein increased significantly (all P<0.05). 740Y-P could partially reverse the inhibitory effect of GKB on HGC-27 cells (all P<0.05). Tumor-bearing nude mouse experience showed that GKB could significantly inhibit the growth of nude mouse transplanted tumors of HGC-27 cells (P<0.05) and downregulate the expressions of PI3K/Akt/mTOR pathway-related proteins. Conclusion: GKB may inhibit the proliferation, migration and invasion and promote the apoptosis of gastric cancer HGC-27 cells by blocking the PI3K/Akt/mTOR signaling pathway.

甘肃省外科肿瘤分子诊断与精准治疗重点实验室项目（No. 2019GSZDSYS04）