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人羊膜上皮细胞通过 TGF-β1 介导的细胞周期阻滞抑制上皮性卵巢癌细胞的生长。

Human amniotic epithelial cells inhibit growth of epithelial ovarian cancer cells via TGF‑β1-mediated cell cycle arrest.

机构信息

The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, P.R. China.

出版信息

Int J Oncol. 2017 Nov;51(5):1405-1414. doi: 10.3892/ijo.2017.4123. Epub 2017 Sep 14.

Abstract

It is reported that human amniotic epithelial cells (hAECs) endow intrinsic antitumor effects on certain kinds of cancer. This research was designed to evaluate whether hAECs endowed potential anticancer properties on epithelial ovarian cancer (EOC) cells in vivo and in vitro, which has not been reported before. In this study, we established a xenografted BALB/c nude mouse model by subcutaneously co-injecting ovarian cancer cell line, SK-OV-3, and hAECs for 28 days. In ex vivo experiments, CCK‑8 cell viability assay, real-time PCR, cell counting assay, cell cycle analysis and immunohistochemistry (IHC) assay were used to detect the effects of hAEC‑secreted factors on the proliferation and cell cycle progression of EOC cells. A cytokine array was conducted to detect anticancer-related cytokines released from hAECs. Human recombinant TGF‑β1 and TGF‑β1 antibody were used to treat EOC cells and analyzed whether TGF‑β1 contributed to the cell cycle arrest. Results from in vivo and ex vivo experiments showed that hAEC-secreted factors and rhTGF‑β1 decreased proliferation of EOC cells and induced G0/G1 cell cycle arrest in cancer cells, which could be partially reversed by excess TGF‑β1 antibody. These data indicate that hAECs endow potential anticancer properties on epithelial ovarian cancer in vivo and in vitro which is partially mediated by hAEC‑secreted TGF‑β1-induced cell cycle arrest. This study suggests a potential application of hAEC‑based therapy against epithelial ovarian cancer.

摘要

据报道,人羊膜上皮细胞(hAECs)对某些类型的癌症具有内在的抗肿瘤作用。本研究旨在评估 hAECs 是否对体内和体外的上皮性卵巢癌(EOC)细胞具有潜在的抗癌特性,这在以前尚未报道过。在这项研究中,我们通过皮下共注射卵巢癌细胞系 SK-OV-3 和 hAECs 建立了一个 28 天的异种移植 BALB/c 裸鼠模型。在离体实验中,使用 CCK-8 细胞活力测定、实时 PCR、细胞计数测定、细胞周期分析和免疫组织化学(IHC)测定来检测 hAEC 分泌因子对 EOC 细胞增殖和细胞周期进程的影响。进行细胞因子阵列以检测 hAEC 释放的抗癌相关细胞因子。用人重组 TGF-β1 和 TGF-β1 抗体处理 EOC 细胞,并分析 TGF-β1 是否有助于细胞周期停滞。体内和体外实验的结果表明,hAEC 分泌的因子和 rhTGF-β1 降低了 EOC 细胞的增殖,并诱导癌细胞中的 G0/G1 细胞周期停滞,这可以部分被过量的 TGF-β1 抗体逆转。这些数据表明,hAECs 对体内和体外的上皮性卵巢癌具有潜在的抗癌特性,这部分是由 hAEC 分泌的 TGF-β1 诱导的细胞周期停滞介导的。这项研究为基于 hAEC 的治疗上皮性卵巢癌提供了一种潜在的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c886/5642391/09beb7620635/IJO-51-05-1405-g00.jpg

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