Normal endometrial stromal cells regulate survival and apoptosis signaling through PI3K/AKt/Survivin pathway in endometrial adenocarcinoma cells in vitro
Normal endometrial stromal cells regulate survival and apoptosis signaling through PI3K/AKt/Survivin pathway in endometrial adenocarcinoma cells in vitro
复制标题
DOI：
10.1016/j.ygyno.2011.07.004
复制
发表时间：
2011-11-01
影响因子：
4.7
通讯作者：
Zhao, Xingbo
中科院分区：
文献类型：
--
作者：
Shi, Min;Zhang, Hui;Zhao, Xingbo
Objective.间质-肿瘤通讯在肿瘤发生中起重要作用。在本研究中，我们研究了正常间质细胞对子宫内膜癌细胞存活和凋亡信号的影响，并进一步探讨了这种通信中可能的机制。利用原代培养的正常子宫内膜间质细胞和子宫内膜腺癌细胞系石川细胞，建立了二维共培养体系，观察子宫内膜癌间质细胞与肿瘤细胞的相互作用。采用KIT法、细胞计数法和集落形成实验，分析了不同条件下气孔细胞对石川细胞生长和增殖的影响。采用western blot方法检测不同条件下基质细胞对石川细胞PI 3 K/AKt/Survivin信号通路活性的影响。采用免疫组化方法检测Survivin在正常子宫内膜和子宫内膜腺癌中的表达。结果显示，在Matrigel上生长的正常子宫内膜间质细胞的旁分泌因子可反复抑制子宫内膜癌细胞株石川中PI 3 K/AKt/Survivin信号通路的活性，而在子宫内膜腺癌中PI 3 K/AKt/Survivin信号通路的活性增强，并在子宫内膜癌细胞株石川中起重要作用。正常子宫内膜间质细胞的旁分泌因子可通过PI 3 K/AKt/Survivin信号通路调节细胞的存活和凋亡，从而抑制子宫内膜刺激的石川细胞增殖。(C)2011 Elsevier Inc. All rights reserved.
Objective. Stroma-tumor communication plays an important role in the genesis of neoplasia. In the current study, we investigated the effect of normal stromal cells on the survival and apoptosis signaling of endometrial cancer cells and further explored the possible mechanism implied in this communication.Methods. Using primarily cultured normal endometrial stromal cells and an endometrial adenocarcinoma cell line, Ishikawa cells, we established a 2D-coculture system to observe the stromal cell-tumor cell crosstalk in endometrial carcinomas. Using methyl thiazolyl tetrazolium (KIT) assays, cell counting and colony formation assays, we analyzed the effect of stomal cells on the growth and proliferation of Ishikawa cells under different conditions. Using western blot analysis, we determined the effect of stromal cells on the activity of PI3K/AKt/Survivin signaling in Ishikawa cells under different conditions. Using immunohistochemistry analysis, we determined the expression of Survivin in normal endometria and endometrial adenocarcinomas.Results. We found that the paracrine factors from normal endometrial stromal cells grown on Matrigel repeatedly and significantly decreased hormone-stimulated activity of PI3K/AKt/Survivin signaling in Ishikawa cells, which were proved to be increased in endometrial adenocarcinoma and essential in hormone-induced cell growth in Ishikawa cells.Conclusion. Paracrine factors from normal endometrial stromal cells can inhibit hormone-stimulated cell proliferation in Ishikawa cells by regulating cell survival and apoptosis through PI3K/AKt/Survivin signaling. (C) 2011 Elsevier Inc. All rights reserved.