The Synergistic Effects of Metformin with Pitavstatin Against MDA-MB-468 Breast Cancer Cells

Document Type : Research Articles

Authors

1 Faculty of Postgraduate Studies and Scientific Research, University of AL-Butana, Ruffaa, Sudan.

2 Department of Biochemistry, Faculty of Medicine, University of AL-Butana, Ruffaa, Sudan.

3 Department of Biological Sciences and Biotechnology, Faculty of Sciences, Islamic University of Gaza, Palestine.

4 Department of Medical Sciences, University College of Science and Technology- Khan Yunis, Palestine.

Abstract

Background: Breast cancer is the most common malignancy among women and a leading cause of cancer-related mortality worldwide. Current therapeutic strategies are associated with several limitations, including cytotoxic side effects and multidrug resistance. As a result, a shift toward drugs with fewer adverse effects and greater efficacy must occur. Recent studies have demonstrated the anticancer potential of both metformin and pitavastatin. This study aimed to investigate the synergistic effects of their combination on MDA-MB-468 triple-negative breast cancer cells. Materials and Methods: The MTT assay was performed to assess the cytotoxicity of metformin and pitavastatin on MDA-MB-468 breast cancer cells. The anti-proliferative effects of the combined treatment were assessed using the trypan blue assay and the clonogenic assay. Additionally, a scratch assay was used to evaluate the migration ability of MDA-MB-468 cells after treatment with metformin and pitavastatin treatments. Results: Both metformin and pitavastatin significantly reduced the viability of MDA-MB-468 cells in a time- and dose-dependent manner. Metformin exhibited an IC₅₀ value of 0.92mM, while pitavastatin showed an IC₅₀ of 1.72µM. Notably, the combined treatment produced a stronger antiproliferative effect compared to either drug alone. Trypan blue data revealed a higher rate of cell death following combination therapy. Furthermore, colony formation was completely inhibited (100%) by the combined treatment compared with to the control group. The scratch assay demonstrated that the combination significantly suppressed cell migration, indicating a synergistic anti-migratory effect. Conclusions: These findings indicate that the combination of metformin and pitavastatin exerts a synergistic anticancer effect against MDA-MB-468 breast cancer cells and may represent a promising therapeutic strategy for triple-negative breast cancer.

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