摘要
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。
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 C33A,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,100μmol/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 C33A 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(50μmol/Land 100μmol/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 an
作者
潘琴
王纯
杨燕峰
陶肖馨
蔡丽彬
方瑛
PAN Qin;WANG Chun;YANG Yanfeng;TAO Xiaoxin;CAI Libin;FANG Ying(Liyang Hospital Affiliated to Nantong University,Liyang 213300,China;Jiangsu Cancer Hospital,Nanjing 210000,China)
出处
《病毒学报》
CAS
CSCD
北大核心
2021年第5期1060-1065,共6页
Chinese Journal of Virology
