Tricostantin A inhibits self-renewal of breast cancer stem cells in vitro
- VernacularTitle:曲古菌素A抑制乳腺肿瘤干细胞的自我更新
- Author:
Li PENG
1
;
Fuxi LI
;
Wenfeng SHAO
;
Jingbo XIONG
Author Information
1. 南方医科大学基础医学院细胞生物学教研室
- Keywords:
cancer stem cells;
breast cancer;
histone deacetylase inhibitor;
Nanog
- From:
Journal of Southern Medical University
2013;(10):1421-1426
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of tricostantin A (TSA) on self-renewal of breast cancer stem cells and explore the mechanisms. Methods Breast cancer cell lines MDA-MB-468, MDA-MB-231, MCF-7 and SKBR3 were cultured in suspension and treated with different concentrations of TSA for 7 days, using 0.1% DMSO as the control. Secondary mammosphere formation efficiency and percentage of CD44+/CD24-sub-population in the primary mammospheres were used to evaluate the effects of TSA on self-renewal of breast cancer stem cells. The breast cancer stem cell surface marker CD44+/CD24- and the percentage of apoptosis in the primary mammospheres were assayed using flow cytometry. The mRNA expressions of Nanog, Sox2 and Oct4 in the primary mammospheres were assayed with quantitative PCR. Results TSA at both 100 and 500 nmol/L, but not at 10 nmol/L, partially inhibited the self-renewal of breast cancer stem cells from the 4 cell lines. TSA at 500 nmol/L induced cell apoptosis in the primary mammospheres. TSA down-regulated the mRNA expression of Nanog and Sox2 in the primary mammospheres. Conclusions TSA can partially inhibit the self-renewal of breast cancer stem cells through a mechanism involving the down-regulation of Nanog and Sox2 expression, indicating the value of combined treatments with low-dose TSA and other anticancer drugs to achieve maximum inhibition of breast cancer stem cell self-renewal. The core transcriptional factor of embryonic stem cells Nanog and Sox2 can be potential targets of anticancer therapy.
