人网膜脂肪间充质干细胞通过 STAT3 信号通路增强卵巢癌细胞自噬。

Human omental adipose-derived mesenchymal stem cells enhance autophagy in ovarian carcinoma cells through the STAT3 signalling pathway.

机构信息

Department of Obstetrics and Gynecology, the Affiliated Hospital of Qingdao University, Qingdao, China.

Department of Orthopaedic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China.

出版信息

Cell Signal. 2020 May;69:109549. doi: 10.1016/j.cellsig.2020.109549. Epub 2020 Jan 24.

DOI:10.1016/j.cellsig.2020.109549

PMID:31987780

Abstract

BACKGROUND

Our previous study showed that human omental adipose-derived stem cells (ADSCs) promote ovarian cancer growth and metastasis. In this study, the role of autophagy in the ovarian cancer-promoting effects of omental ADSCs was further determined.

METHODS

The growth and invasion of ovarian cancer cells were detected by CCK-8 and Transwell assays, respectively. The autophagy of ovarian cancer cells transfected with MRFP-GFP-LC3 adenoviral vectors was evaluated by confocal microscopy and western blot assay. Transfection of STAT3 siRNA was used to inhibit the expression of STAT3.

RESULTS

Our results show that autophagy plays a vital role in ovarian cancer and is promoted by ADSCs. Specifically, we show that proliferation and invasion are correlated with autophagy induction by ADSCs in two ovarian cancer cell lines under hypoxic conditions. Mechanistically, ADSCs activate the STAT3 signalling pathway, thereby promoting autophagy. Knockdown of STAT3 expression using siRNA decreased hypoxia-induced autophagy and decreased the proliferation and metastasis of ovarian cancer cells.

CONCLUSION

Taken together, our data indicate that STAT3-mediated autophagy induced by ADSCs promotes ovarian cancer growth and metastasis.

摘要

背景

我们之前的研究表明，人网膜脂肪来源的干细胞（ADSCs）促进卵巢癌细胞的生长和转移。在这项研究中，进一步确定了自噬在网膜 ADSCs 促进卵巢癌作用中的角色。

方法

通过 CCK-8 和 Transwell 分析分别检测卵巢癌细胞的生长和侵袭。通过共聚焦显微镜和 Western blot 分析评估转染了 MRFP-GFP-LC3 腺病毒载体的卵巢癌细胞的自噬情况。转染 STAT3 siRNA 用于抑制 STAT3 的表达。

结果

我们的结果表明，自噬在卵巢癌中起着至关重要的作用，并且受到 ADSCs 的促进。具体而言，我们表明，在两种卵巢癌细胞系中，在缺氧条件下，ADSCs 通过诱导自噬促进增殖和侵袭。ADSCs 激活 STAT3 信号通路，从而促进自噬。使用 siRNA 敲低 STAT3 表达可降低缺氧诱导的自噬，并减少卵巢癌细胞的增殖和转移。