IGF1调控PI3K/AKT信号通路对卵巢癌细胞增殖和侵袭的影响

Effect of IGF1 on proliferation and invasion of ovarian cancer cells byregulating PI3K/AKT signaling pathway

目的研究胰岛素样生长因子1(insulin-like growth factor-1,IGF1)在卵巢癌及癌旁组织中的表达情况及其对卵巢癌细胞增殖和侵袭的影响,以探索IGF1参与卵巢癌发生发展的机制。方法选取2019年3月至2021年9月于海南医学院第一附属医院进行手术切除治疗的卵巢癌患者27例,收集其肿瘤及癌旁组织,分析不同组织、不同分期中IGF1、PI3K的表达水平差异,比较人卵巢癌细胞系Skov-3、Caov-3、PA-1中IGF1表达水平差异;将si-IGF1、si-NC分别转染至Skov-3细胞,分为si-IGF1组和si-NC组,比较各组细胞IGF1、p-PI3K、p-AKT表达水平及增殖和侵袭能力差异;在两组细胞中加入PI3K激动剂(Recilisib)后,比较各组细胞IGF1、p-PI3K、p-AKT表达水平以及增殖和侵袭能力差异。采用qRT-PCR检测IGF1基因表达水平,Western blot检测p-PI3K、p-AKT蛋白表达水平,CCK8检测细胞增殖水平,Transwell检测细胞侵袭水平。结果与癌旁组织比较,肿瘤组织IGF1和PI3K表达水平升高;与Ⅰ~Ⅱ期比较,Ⅲ期肿瘤组织中IGF1和PI3K表达水平升高,且在肿瘤组织中IGF1和PI3K的表达水平呈正相关。与Caov-3和PA-1细胞比较,Skov-3细胞中IGF1表达水平升高。与si-NC组比较,si-IGF1组IGF1基因表达水平、p-PI3K和p-AKT蛋白表达水平、细胞增殖和侵袭能力降低。与si-NC组和si-IGF1组比较,si-NC+Recilisib和si-IGF1+Recilisib组p-PI3K、p-AKT蛋白表达水平升高,细胞增殖和侵袭能力增加。结论IGF1可通过增强PI3K/AKT信号通路促进卵巢癌细胞增殖和侵袭,最终介导肿瘤恶化。

Objective To study the expression of insulin-like growth factor 1(ICF1)in the ovarian cancer and adjacent tissues and its effect on the proliferation and invasion of ovarian cells,so as to explore the mechanism of IGF1 involved in the development of ovarian cancer.Methods A total of 27 patients with ovarian cancer who underwent surgical resection in the First Afiliated Hospital of Hainan Medical University from March 2019 to September 2021 were selected,to collect tumor and adjacent tissues and analyze the differences in the expression levels of IGF1 and PI3K in different tissues and stages.The expression of IGF1 in human ovarian cancer cell lines Skov-3,Caov-3 and PA-1 was compared.The si-ICF1 and si-NC were transfected into Skov-3 cells and divided into si-ICF1 group and si-NC group.The expression levels of IGFI,p-PI3K and p-AKT,as well as the proliferation and invasion ability of each group were compared.After adding PI3K agonist(Recilisib)to the two groups of cells,the differences in the expression levels of ICF1,p-PI3K,p-AKT,proliferation and invasion abilities of the cells in each group were compared.The expression level of IGF1 gene was detected by qRT-PCR,the expression levels of p-PI3K and p-AKT proteins were detected by Western blot,the cell proliferation level was detected by CCK8,and the cell invasion level was detected by Transwell.Results The expression levels of IGF1 and PI3K in tumor tissues were higher than those in adjacent tissues;Compared with stage Ⅰ~Ⅱ,the expression levels of IGFI and PI3K in stage Ⅲ tumor tissues were increased,and the expression levels of IGFl and PI3K in tumor tissues were positively correlated in tumor tissues.Compared with Caov-3 and PA-1 cells,the expression levels of ICF1 were elevated in Skov-3 cells.Compared with the si-NC group,the expression levels of IGF1 gene,p-PI3K and p-AKT protein,cell proliferation and invasion ability were decreased in the si-IGF1 group,Compared with the si-NC and si-IGF1 group,the p-PI3K and p-AKT protein expression levels were elevated in the si-NC+Recilisib and si-ICF1+Recilisib groups,and cell proliferation and invasion ability were increased.Conclusion IGF1 promotes ovarian cancer cell proliferation and invasion through enhancing the PI3K/AKT signaling pathway,which ultimately mediates tumor progression.