1. Anti-Proliferative and Apoptotic Activities of Müllerian Inhibiting Substance Combined with Calcitriol in Ovarian Cancer Cell Lines
- Author
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Hee Jung Kim, Young Tae Kim, Young Sik Choi, Seok Kyo Seo, Jae Wook Kim, Eun Ji Nam, Hyuck Dong Han, Yeon Soo Jung, Sang Wun Kim, and Sunghoon Kim
- Subjects
0301 basic medicine ,calcitriol ,Anti-Mullerian Hormone ,Calcitriol ,endocrine system diseases ,Receptors, Peptide ,antiproliferation ,Cell Survival ,Apoptosis ,Enzyme-Linked Immunosorbent Assay ,DNA Fragmentation ,Biology ,03 medical and health sciences ,Ovarian cancer ,Cell Line, Tumor ,medicine ,Humans ,Viability assay ,Extracellular Signal-Regulated MAP Kinases ,Cell Proliferation ,Ovarian Neoplasms ,Cell growth ,Caspase 3 ,Cell Cycle ,General Medicine ,Cell cycle ,Caspase 9 ,Growth Inhibitors ,Müllerian inhibiting substance ,030104 developmental biology ,Oncology ,Cell culture ,Cancer research ,DNA fragmentation ,Original Article ,Female ,Signal transduction ,Receptors, Transforming Growth Factor beta ,medicine.drug ,Signal Transduction - Abstract
Purpose This study aimed to investigate whether Mullerian 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-regulated the expression of B-cell lymphoma 2 (Bcl-2), and up-regulated the expressions of Bcl-2 associated X protein, 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.
- Published
- 2015