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Anti-Proliferative and Apoptotic Activities of Müllerian Inhibiting Substance Combined with Calcitriol in Ovarian Cancer Cell Lines
- Source :
- Yonsei Medical Journal
- Publication Year :
- 2015
- Publisher :
- Yonsei University College of Medicine, 2015.
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 19762437 and 05135796
- Volume :
- 57
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Yonsei Medical Journal
- Accession number :
- edsair.doi.dedup.....336409f2c7169d9ef65e149b557c7cf1