柚皮苷通过PI3K/Akt/mTOR通路调控宫颈癌细胞活力、侵袭和迁移  

Naringin regulates vitality,invasion and migration of cervical cancer cells through PI3K/Akt/mTOR pathway

作　　者：李明霞 汪玲 刘秀玲 李金锋 LI Mingxia;WANG Ling;LIU Xiuling;LI Jinfeng(Zhumadian Central Hospital,Zhumadian 463000,China)

机构地区：[1]驻马店市中心医院,河南驻马店463000

出　　处：《中草药》2025年第6期2017-2024,共8页Chinese Traditional and Herbal Drugs

摘　　要：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.

关 键 词：柚皮苷 宫颈癌 PI3K/Akt/mTOR通路 迁移 侵袭 凋亡 

分 类 号：R285.5[医药卫生—中药学]