IGF信号轴在卵巢癌干细胞样细胞增殖状态转换及预防卵巢癌复发中的作用-东南大学学报医学版

IGF信号轴在卵巢癌干细胞样细胞增殖状态转换及预防卵巢癌复发中的作用

单位：1. 东南大学医学院, 江苏南京 210009;
2. 东南大学附属中大医院妇产科, 江苏南京 210009

关键词：胰岛素样生长因子-1 胰岛素样生长因子-1受体 NVP-AEW541 卵巢癌干细胞样细胞

分类号：R737.31

出版年·卷·期（页码）：2016·35·第五期（736-741）

摘要：

目的：探究胰岛素样生长因子（IGF）信号轴在促进卵巢癌干细胞样细胞增殖和抗凋亡中的作用，探讨基于IGF信号轴的IGF-1R抑制剂的靶向治疗和寻求降低卵巢癌化疗后复发的可能途径。方法：采用CD117⁺ CD44⁺ A2780卵巢癌细胞株，使用免疫细胞化学的方法检测IGF信号轴中IGF-1、IGF-2和IGF-1R在CD117⁺ CD44⁺ A2780细胞中的表达；利用MTT法检测IGF-1对CD117⁺ CD44⁺ A2780细胞的促增殖活性，配制IGF-1的质量浓度分别为10、25、40、55 ng·ml^-1，另设空白对照，从中筛选出加入外源IGF-1的适宜质量浓度用于后续实验中；再将实验分为3组，即IGF-1刺激组、NVP抑制组和空白组。通过流式细胞术检测3组细胞在药物处理48 h后的细胞周期分布和凋亡率情况。结果：IGF信号轴组件IGF-1、IGF-2和IGF-1R均表达在CD117⁺ CD44⁺ A2780细胞的细胞膜上和细胞质中；MTT检测发现当外源IGF-1质量浓度为40 ng·ml^-1时对CD117⁺ CD44⁺ A2780细胞的促分裂增殖作用最明显；IGF-1刺激组较空白组增殖明显活跃，凋亡率降低（P<0.05）；NVP抑制组较空白组增殖明显减少，凋亡率增高（P<0.05）。结论：IGF信号轴与卵巢癌化疗后的复发密切相关，IGF-1在卵巢癌干细胞样细胞转换增殖状态和对抗凋亡中发挥着重要作用；NVP阻断IGF-1R的作用可有效抑制卵巢癌干细胞样细胞从休眠状态启动分裂增殖；IGF信号轴组件可作为卵巢癌治疗及化疗后预防复发的靶点。

Objective: To explore the role of IGF signal axis in promoting cell proliferation and anti-apoptosis of CD117⁺ CD44⁺ A2780, the ovarian cancer stem cell-like cells, discussing the targeting therapy based on IGF signal axis of IGF-1R and looking for possible ways to reduce the recurrence of ovarian cancer after chemotherapy. Materials and Methods: This experiment used CD117⁺ CD44⁺ A2780 ovarian cancer cell line, the expression of IGF-1, IGF-2 and IGF-1R of IGF signal axis in CD117⁺ CD44⁺ A2780 were detected by immune histochemical method; cells proliferation which was promoted by IGF-1 was measured by MTT assay in CD117⁺ CD44⁺ A2780, the concentration of IGF-1 was respectively 10, 25, 40, 55 ng·ml^-1 and blank group. The suitable concentration of IGF-1 was selected and used in subsequent experiment; then the experiment was divided into three group: IGF-1 stimulate group, NVP inhibit group and blank group, the cell cycle and apoptosis rate were analyzed by flow cytometry after 48 h drug treatment. Results: IGF-1, IGF-2 and IGF-1R of IGF signal axis expressed in CD117⁺ CD44⁺ A2780's cell membrane and cytoplasm; MTT test experimented on CD117⁺ CD44⁺ A2780 selected the suitable concentration of the four group of exogenous IGF-1, with a concentration of 40 ng·ml^-1 obviously promoting the proliferation; flow cytometry showed more active proliferation and a decreased apoptosis rate in IGF-1 stimulating group compared with the blank group(P<0.05); NVP inhibiting group, compared with blank group, inhibited proliferation and increased apoptosis rate(P<0.05). Conclusion: IGF signal axis has close relationship with the recurrence of ovarian cancer after chemotherapy; IGF-1 plays an important role in transforming the state of proliferation and anti-apoptosis; NVP can block the effect of IGF-1, stop ovarian cancer stem cell-like cells transforming from quiescent state to growth state; IGF axis can be used as target proteins in ovarian cancer treatment and prevention of recurrence after chemotherapy.

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