Combining the mammalian target of rapamycin inhibitor, rapamycin, with resveratrol has a synergistic effect in multiple myeloma

Rapamycin is known to inhibit the mammalian target of rapamycin complex (mTORC)1 signaling pathway, but it is unable to effectively inhibit mTORC2, resulting in activation of protein kinase B in multiple myeloma (MM) cell lines. Additionally, certain studies have suggested that resveratrol has an effect on human MM cells, and that rapamycin in combination with resveratrol may be useful in cancer therapy. The present study aimed to investigate the combined treatment effect of resveratrol and rapamycin on the MM MM1.S cell line. The results demonstrated that combined treatment with rapamycin and resveratrol effectively inhibited cell viability in the MM1.S cell line through inhibition of the mTORC1 and mTORC2 signaling pathways, compared with resveratrol or rapamycin monotherapy. In addition, cyclin D1 levels were decreased and the activation of caspase-3 and poly (ADP-ribose) polymerase was increased. These results suggested that downregulation of the mTOR signaling cascades is likely to be a crucial mediator in the impairment of viability and the induction of apoptosis resulting from combined therapy with resveratrol and rapamycin in MM1.S cells.