目的 研究柚皮苷對人宮頸癌HeLa細(xì)胞活力、遷移、侵襲、凋亡和磷脂酰肌醇3激酶（phosphatidylinositol 3-kinase，PI3K）/蛋白激酶B（protein kinase B，Akt）/哺乳動物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）信號的影響及作用機(jī)制。方法 取對數(shù)生長期的HeLa細(xì)胞，設(shè)置對照組和柚皮苷低、中、高劑量組，藥物作用24 h后，細(xì)胞計數(shù)試劑盒-8（cell counting kit-8，CCK-8）法檢測細(xì)胞活力，流式細(xì)胞術(shù)檢測細(xì)胞凋亡，Transwell實驗檢測細(xì)胞遷移、侵襲，Western blotting法檢測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）的表達(dá)，以及添加PI3K激活劑胰島素樣生長因子1（insulin-like growth factor 1，IGF-1）后對柚皮苷作用的影響。構(gòu)建荷瘤小鼠模型，檢測柚皮苷對腫瘤生長的影響。結(jié)果 與對照組比較，柚皮苷可顯著抑制HeLa細(xì)胞的活力（P＜0.05、0.001），促進(jìn)細(xì)胞凋亡（P＜0.05、0.001），細(xì)胞的遷移、侵襲能力也顯著降低（P＜0.05、0.001），且具有劑量相關(guān)性；柚皮苷能夠顯著降低PI3K、Akt、mTOR磷酸化蛋白表達(dá)水平（P＜0.01、0.001），而PI3K激活劑IGF-1可顯著逆轉(zhuǎn)柚皮苷對PI3K、Akt、mTOR磷酸化蛋白表達(dá)水平的影響（P＜0.001）。柚皮苷能夠顯著抑制體內(nèi)腫瘤的生長（P＜0.05、0.01）。結(jié)論 柚皮苷以劑量相關(guān)的方式通過PI3K/Akt/mTOR調(diào)控宮頸癌細(xì)胞活力、遷移和侵襲，促進(jìn)細(xì)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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