Anti-proliferative and apoptotic activities of Müllerian inhibiting substance combined with calcitriol in ovarian cancer cell lines

Abstract

Purpose

This study aimed to investigate whether Müllerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis.

Materials and Methods

OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway.

Results

The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time- dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulating the expression of B-cell lymphoma 2 (Bcl-2); and up-regulating the expression of Bcl-2 associated X protein (BAX), caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway.

Conclusion

These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of OCa.