Adelipour Maryam, Allameh Abdolamir, Sheikhi Abdolkarim, Ranjbaran Mina, Naghashpour Mahshid, Nazeri Zahra, Mojiri-Forushani Hoda, Golabi Sahar
Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Iran J Basic Med Sci. 2021 Jan;24(1):98-107. doi: 10.22038/ijbms.2020.51461.11678.
Autophagy is an intracellular degradation system of damaged proteins and organelles; however, the role of autophagy in the progression of cancer remains unclear. In recent years, mesenchymal stem cell (MSC)-based approaches have attracted considerable attention for anti-cancer therapy. The present study aimed to examine the interaction of MSCs with the breast cancer cells under autophagy-induced conditions.
In this study, MSCs isolated from human adipose tissue were co-cultured with MDA-MB 231, a breast cancer cell line, and the autophagy process was induced by tunicamycin treatment. The cell viability was monitored by the MTT assay, and the cells were recovered at different time intervals (24 or 48 hours) to determine autophagy markers such as Beclin, mTOR and the ratio of LC3II/I expression. Additionally, the animal study was conducted using a mouse model of breast cancer treated with isogenic adipose-derived MSCs, and the expression of Beclin and Ki67 was determined using immunohistochemistry in breast tumor tissue.
In cancer cells co-cultured with MSCs, the cell proliferation was increased, the Beclin expression and the LC3II/I protein ratio were decreased, and the mTOR expression was increased in MDA-MB 231 upon co-cultured with MSCs. Direct injection of MSCs to a mouse model of breast cancer showed an increase in tumor volume, an increase in the accumulation of Ki67 and a decrease in the Beclin expression in tumor tissues.
The data may suggest that suppressed autophagy in breast cancer cells is probably a mechanism by which MSCs can induce cancer cell proliferation.
自噬是一种细胞内对受损蛋白质和细胞器的降解系统；然而，自噬在癌症进展中的作用仍不清楚。近年来，基于间充质干细胞（MSC）的方法在抗癌治疗中引起了相当大的关注。本研究旨在检测在自噬诱导条件下MSC与乳腺癌细胞之间的相互作用。
在本研究中，将从人脂肪组织中分离出的MSC与乳腺癌细胞系MDA-MB 231共培养，并用衣霉素处理诱导自噬过程。通过MTT法监测细胞活力，并在不同时间间隔（24或48小时）收集细胞以测定自噬标志物，如Beclin、mTOR和LC3II/I表达比值。此外，使用同基因脂肪来源的MSC处理的乳腺癌小鼠模型进行动物研究，并通过免疫组织化学法测定乳腺肿瘤组织中Beclin和Ki67的表达。
与MSC共培养的癌细胞中，MDA-MB 231细胞的增殖增加，Beclin表达和LC3II/I蛋白比值降低，mTOR表达增加。将MSC直接注射到乳腺癌小鼠模型中显示肿瘤体积增大，肿瘤组织中Ki67积累增加，Beclin表达降低。
数据可能表明，乳腺癌细胞中自噬的抑制可能是MSC诱导癌细胞增殖的一种机制。
