目的 研究柚皮苷对人宫颈癌HeLa细胞活力、迁移、侵袭、凋亡和磷脂酰肌醇3激酶（phosphatidylinositol 3-kinase，PI3K）/蛋白激酶B（protein kinase B，Akt）/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）信号的影响及作用机制。方法 取对数生长期的HeLa细胞，设置对照组和柚皮苷低、中、高剂量组，药物作用24 h后，细胞计数试剂盒-8（cell counting kit-8，CCK-8）法检测细胞活力，流式细胞术检测细胞凋亡，Transwell实验检测细胞迁移、侵袭，Western blotting法检测PI3K、磷酸化PI3K（phosphorylated PI3K，p-PI3K）、Akt、磷酸化Akt（phosphorylated Akt，p-Akt）、mTOR、磷酸化mTOR（phosphorylated mTOR，p-mTOR）的表达，以及添加PI3K激活剂胰岛素样生长因子1（insulin-like growth factor 1，IGF-1）后对柚皮苷作用的影响。构建荷瘤小鼠模型，检测柚皮苷对肿瘤生长的影响。结果 与对照组比较，柚皮苷可显著抑制HeLa细胞的活力（P＜0.05、0.001），促进细胞凋亡（P＜0.05、0.001），细胞的迁移、侵袭能力也显著降低（P＜0.05、0.001），且具有剂量相关性；柚皮苷能够显著降低PI3K、Akt、mTOR磷酸化蛋白表达水平（P＜0.01、0.001），而PI3K激活剂IGF-1可显著逆转柚皮苷对PI3K、Akt、mTOR磷酸化蛋白表达水平的影响（P＜0.001）。柚皮苷能够显著抑制体内肿瘤的生长（P＜0.05、0.01）。结论 柚皮苷以剂量相关的方式通过PI3K/Akt/mTOR调控宫颈癌细胞活力、迁移和侵袭，促进细胞凋亡。

Objective To study the effects of naringin on the viability, migration, invasion, apoptosis and expression of phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signal of human cervical cancer HeLa cells and its mechanism. Methods Cervical cancer HeLa cells at logarithmic growth stage were selected, and control group, low-, medium- and high-concentration naringin group were set up. After 24 h of drug intervention, cell viability was detected by cell counting kit-8 (CCK-8) method, cell apoptosis was detected by flow cytometry, cell migration and invasion were detected by Transwell assay. Western blotting assay was used to detect the expression of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), mTOR, phosphorylated mTOR (p-mTOR), and the effect of addition of PI3K activator insulin-like growth factor 1 (IGF-1) on naringin action. A tumor-bearing mice model was established in vivo to detect the effect of naringin on tumor growth. Results Compared with the blank control group, naringenin could inhibit the activity of HeLa cells (P < 0.05, 0.001), promote apoptosis (P < 0.05, 0.001), and significantly reduce the migration and invasion ability of HELA cells in a dose-dependent manner (P < 0.05, 0.001). Naringenin could reduce the phosphorylation levels of PI3K, Akt and mTOR (P < 0.01, 0.001). IGF-1 could significantly reverse the phosphorylation of PI3K, Akt and mTOR by naringin (P < 0.001). The treatment with naringin significantly inhibited the growth of tumors in vivo (P < 0.05, 0.01). Conclusion Naringin can regulate the viability, invasion and migration of cervical cancer cells through PI3K/Akt/mTOR in a dose-dependent manner, and promote cell apoptosis.

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