胰岛素样生长因子受体通路对卵巢癌移植瘤中休眠细胞启动增殖的调控  

Insulin-like Growth Factor Receptor Signaling Pathway Modulating Proliferation of Dormant Cells in Ovarian Cancer Xenografts

作　　者：吴小华 周楠[1] 杨波[1] 杨旭[2] 张丁丁[3] 

机构地区：[1]白求恩国际和平医院,河北石家庄050082 [2]秦皇岛市第一医院,河北秦皇岛066000 [3]中国中医科学院望京医院,北京100102

出　　处：《肿瘤学杂志》2014年第3期190-196,共7页Journal of Chinese Oncology

摘　　要：[目的]观察胰岛素样生长因子(IGF)受体通路对卵巢癌休眠肿瘤细胞启动增殖的调控机制。[方法]采用免疫细胞化学法检测SKOV3-PKH26hi细胞IGF-1、IGF-2和IGF-1R的表达,酶联免疫吸附测定法(ELISA)测定细胞培养液中IGF-1和IGF-2的浓度,细胞计数和MTT法测定加入外源性IGF-1对SKOV3-PKH26hi细胞增殖的影响,流式细胞术检测细胞IGF-1R和Ki-67的表达、细胞周期和凋亡率,Western blot方法检测细胞p-AKT、p-GSK3β及cyclin B1的表达。[结果]SKOV3-PKH26hi细胞均可以表达IGF-1、IGF-2和IGF-1R;培养液中IGF-1和IGF-2的浓度随培养时间的延长显著升高(P<0.05);IGF-1对SKOV3-PKH26hi细胞能发挥促增殖作用;SKOV3-PKH26hi细胞IGF-1R、Ki-67、p-AKT、p-GSK3β、cyclin B1的表达量随着培养时间的延长而显著增高(P<0.05);随着培养时间的增加SKOV3-PKH26hi细胞G0/G1和G2/M期细胞显著减少(P<0.05),S期细胞显著增加(P<0.05),不同时间点的凋亡率差异无统计学意义(P>0.05)。[结论]SKOV3-PKH26hi细胞存在IGF自分泌,IGF受体通路能够调控卵巢癌休眠细胞的增殖。[Purpose] To investigate the mechanism of insulin-like growth factor（IGF） receptor signaling pathway modulating proliferation of dormant cells in ovarian cancer. [Methods]Expression of IGF-1,IGF-2 and IGF-1R in SKOV3-PKH26hi cells was detected immunocytochemically. Concentration of IGF-1and IGF-2 in the culture medium of SKOV3-PKH26hi cells was evaluated by ELISA. Cell count and MTT assay were used to measure the proliferation of SKOV3-PKH26hi cells with various concentrations of exogenous IGF-1. Flow cytometry was used to analyze the protein expression of IGF-1R,Ki-67,cell cycle and apoptosis of SKOV3-PKH26hi cells. The expression of p-AKT,p-GSK3β and cyclin B1 of SKOV3-PKH26hi cells was determined by Western blot. [Results] Immunocytochemical staining of SKOV3-PKH26hi cells showed staining for IGF-1,IGF-2 and IGF-1R. The protein expression of IGF-1 and IGF-2 in medium was increased with prolonged incubation time（P＆lt;0.05）. IGF-1 increased the proliferation of SKOV3-PKH26hi cells in a dose-dependent manner. The protein expression of IGF-1R,Ki-67,p-AKT,p-GSK3β and cyclin B1 in SKOV3-PKH26hi cells was increased with prolonged incubation time（P＆lt;0.05）. With prolonging culture time,SKOV3-PKH26hi cells showed a reduction of cells in the G0/G1and G2/M phase（P＆lt;0.05）,and accumulation of cells in S phase（P＆lt;0.05）. The apoptotic rates in different culture time were not significant difference（P＆gt;0.05）. [Conclusion] IGF autocrine loop is existed in SKOV3-PKH26hi cells. Insulin-like growth factor receptor signaling pathway could modulate proliferation of dormant cancer cells in epithelial ovarian cancer.

关 键 词：卵巢肿瘤 休眠细胞 胰岛素样生长因子 细胞增殖 

分 类 号：R734.2[医药卫生—肿瘤]