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Evaluation of Effects of Metformin in Primary Ovarian Cancer Cells
Seema Patel1, Neeta Singh, Lalit Kumar
1Department of Biochemistry, AIIMS, New Delhi, India E-mail : singh_neeta26@rediffmail.com, singh_neeta@hotmail.com.
Background:
Ovarian cancer is the third most common cause of cancer in Indian women. Despite an initial 70-80% response rate, most patients relapse within 1-2 years and develop chemoresistance. Hence, identification or repositioning of drugs to resensitise ovarian cancer cells to existing chemotherapy is needed. Traditionally immortalized cell lines have been used in research, but these may contain genetic aberrations and chromosomal abnormalities serving as poor indicators of normal cell phenotype and progression of early-stage disease. The use of primary cells, maintained for only short periods of time in vitro, may serve as the best representative for studying in vivo conditions of the tissues from which they are derived. In this study we have attempted to evaluate the effect of metformin (an antidiabetic drug) in primary ovarian cancer cells because of its promising effect in other solid tumours.
Materials And Methods:
Primary cultures of epithelial ovarian cancer cells established from ascitic fluid of untreated ovarian cancer patients were used. The cells were treated with metformin at doses standardized by MTT assay and its ability to induce apoptosis was studied. The cells were analysed for apoptosis and apoptosis related proteins by flow cytometry and western blotting respectively.
Results:
Metformin induced apoptosis in ovarian cancer cells, provoking cell cycle arrest in the G0/G1 and S phase. It induced apoptosis in ovarian cancer cells by, down-regulating Bcl-2 and up-regulating Bax expression.
Conclusions:
Metformin was able to induce apoptosis in primary ovarian cancer cells by modulating the expression of Bcl-2 family proteins. These data are relevant to ongoing translational research efforts exploring the chemotherapeutic potential of metformin.
Insights
Metformin, an antidiabetic drug, effectively induces apoptosis in primary ovarian cancer cells. This research highlights metformin
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Ovarian cancer is a leading cause of cancer death in Indian women, with high relapse and chemoresistance rates.
- Traditional cell lines may not accurately reflect ovarian cancer's in vivo conditions.
- Primary ovarian cancer cells offer a more representative model for studying drug efficacy.
Purpose of the Study:
- To evaluate the anti-cancer effects of metformin, an antidiabetic drug, on primary ovarian cancer cells.
- To investigate metformin's potential to resensitize chemoresistant ovarian cancer cells.
Main Methods:
- Primary epithelial ovarian cancer cells were isolated from patient ascites.
- Cells were treated with metformin, and apoptosis was assessed.
- Apoptosis-related proteins (Bcl-2, Bax) were analyzed via flow cytometry and western blotting.
Main Results:
- Metformin induced significant apoptosis in primary ovarian cancer cells.
- The drug caused cell cycle arrest in the G0/G1 and S phases.
- Metformin modulated Bcl-2 family proteins, down-regulating Bcl-2 and up-regulating Bax.
Conclusions:
- Metformin effectively induces apoptosis in primary ovarian cancer cells by altering Bcl-2 family protein expression.
- These findings support metformin's potential as a chemotherapeutic agent for ovarian cancer.
- Further translational research is warranted to explore metformin's role in ovarian cancer treatment.
