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高危型人乳头瘤病毒(Human papiloma virus,HPV)感染是宫颈癌的危险因素,HPV16是常见的高危型HPV,与宫颈癌的发病有关,但具体机制未明确。有临床研究报道,宫颈癌组织中HPV16感染与磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B(AKT)表达增加有关,为了阐明PI3K/AKT信号通路及其抑制剂LY294002在HPV感染宫颈癌细胞增殖中的调控作用,本实验培养了HPV16感染的宫颈癌细胞株SiHa、HPV阴性的宫颈癌细胞株C33A、正常宫颈上皮细胞株H8,检测了p-PI3K、p-AKT的表达水平;SiHa细胞分为对照组、50μmol/L及100μmol/L LY294002组,药物干预后检测细胞增殖活力A490值及p-PI3K、p-AKT、c-myc、B淋巴细胞瘤-2基因(Bcl-2)的表达水平;皮下注射SiHa细胞建立移植瘤小鼠模型,分为对照组、25mg/kg、50mg/kg LY294002组,药物干预后取移植瘤称重。结果显示,SiHa细胞中p-PI3K、p-AKT的表达水平均高于C33A、H8细胞;50μmol/L及100μmol/L LY294002组SiHa细胞的A490值及p-PI3K、p-AKT、c-myc、bcl-2的表达水平均低于对照组;25 mg/kg、50 mg/kg LY294002组移植瘤小鼠的移植瘤质量均低于对照组(P<0.05)。以上结果表明HPV16感染的宫颈癌细胞中PI3K/AKT信号通路过度激活具有促增殖作用。本实验阐明了PI3K/AKT通路及其抑制剂LY294002在HPV16感染的宫颈癌细胞增殖中的调控作用,PI3K/AKT通路的激活能够促进HPV16感染的宫颈癌细胞增殖及移植瘤的生长,使用信号通路抑制剂能够抑制细胞增殖及移植瘤生长,未来PI3K/AKT通路可能成为HPV16感染引起宫颈癌的防治靶点。
Abstract：Human papillomavirus(HPV) infection is a risk factor for cervical cancer. Clinical studies have shown that HPV16 infection in cervical cancer is related to increased expression of phosphatidylinositol-3 kinase(PI3K) and protein kinase B(Akt). We wished to elucidate the regulatory role of the PI3K/Akt signaling pathway and its antagonist LY294002 in the proliferation of HPV-infected cervical-cancer cells. We cultured the cervical-cancer cell line SiHa,HPV-negative cervical-cancer cell line C33 A,and normal cervical epithelial cell line H8. Expression of phosphorylated(p)-PI3K and p-AKT was measured. SiHa cells were divided into the control group and LY294002(50μmol/L,100 μmol/L)group. Proliferation activity at absorbance of 490 nm(A490)and expression of p-PI3K,p-AKT,c-myc and b-lymphoma-2 gene(bcl-2)were measured after drug intervention. SiHa cells were injected(s.c.)to establish a transplanted-tumor model in mice,who were divided into the control group and LY294002(25 mg/kg and 50 mg/kg)group. Then,the transplanted tumor was weighed after drug intervention. Expression of p-PI3K and p-AKT in SiHa cells was higher than that in C33 A cells and H8 cells. The A490 level and expression of p-PI3K,p-AKT,c-myc and Bcl-2 in SiHa cells in the two LY294002 groups(50 μmol/Land 100 μmol/L)were lower than those in the control group. The quality of the transplanted tumor in the LY294002 groups(25 mg/kg and 50 mg/kg)was lower than that in the control group(P<0.05). These results indicated that overactivation of the PI3K/Akt signaling pathway in HPV16-infected cervical-cancer cells could promote proliferation. We elucidated,for the first time,the regulatory role of the PI3K/Akt pathway and its antagonist LY294002 in the proliferation of HPV16-infected cervical-cancer cells.Activation of the PI3K/Akt pathway could promote the proliferation of HPV16-infected cervical-cancer cells and the growth of transplanted tumors. Use of signaling-pathway inhibitors can inhibit the proliferation of cells and growth of transplanted tumors. The PI3K/Akt pathway could become the prevention-and-treatment target of HPV16 infection-induced cervical cancer.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.004031
中图分类号:R737.33
引用信息:
[1]潘琴,王纯,杨燕峰,等.PI3K抑制剂LY294002在HPV感染宫颈癌细胞的调节作用[J].病毒学报,2021,37(05):1060-1065.DOI:10.13242/j.cnki.bingduxuebao.004031.
2020-08-09
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2021-08-21