Rapamycin enhances the antiproliferative effect of transforming growth factor-β on MCF-7 human breast cancer cells.

Transforming growth factor-β (TGF-β), a well-known cytokine with pleiotropic biological functions, has an important role in the regulation of cellular proliferation. Rapamycin has specific antagonistic activity on the function of the mammalian target of the rapamycin signaling pathway. The cooperation of TGF-β and rapamycin on the proliferation of Michigan Cancer Foundation (MCF)-7 human breast cancer cells is unclear. The present study demonstrated that TGF-β had a growth-arresting effect on MCF-7 cancer cells. TGF-β stimulation resulted in the upregulation of several cyclin-dependent kinase inhibitors, including p14ARF, p15INK4b, p16INK4a and p21WAF1/CIP1. The present study also demonstrated that rapamycin enhances the antiproliferative effect of TGF-β. The combination of rapamycin and TGF-β induced apoptosis of MCF-7 tumor cells. These findings advance the current understanding of the biological effects of TGF-β and rapamycin.