Hypoxia-Inducible Factor 1-Alpha Regulates Cancer-Inhibitory Effect of Human Mesenchymal Stem Cells.

Abstract

Mesenchymal stem cells (MSCs) have been shown to be able to inhibit cancer cells growth. In this study, we investigate the role and the molecular mechanism of hypoxia-inducible factor 1-alpha (HIF-1α) in inhibition of cancer cell proliferation by human MSCs through depletion and overexpression of HIF-1α in human MSCs. We found that the cell culture medium from HIF-1α-depleted Z3 cells significantly promotes breast cancer MCF-7 cell proliferation and colony formation. The expression of p21 is increased in MCF-7 cells, but p53 level remains unchanged. In contrast, the cultured medium from HIF-1α-overexpressed Z3 cells dramatically inhibits MCF-7 cell proliferation and colony formation. The expression of p21 is inhibited in MCF-7 cells, but p53 does not change. We conclude HIF-1α promotes inhibitory effect of human MCSs on breast cancer cell proliferation and colony formation. This process is tightly correlated with cell cycle protein p21 level in cancer cells.