Metformin Enhances the Sensitivity of Glioblastoma Cancer Cells to Cisplatin through DNA Damage Assessment

Background: Glioblastoma (GBM) stands out as the most prevalent primary brain tumor characterized by its high aggressiveness. Numerous therapeutic approaches have been employed, and the utility of combination therapies has been substantiated, particularly in GBM treatment. Cisplatin, an anticancer chemotherapeutic agent, is employed for the management of various malignancies, including GBM; however, it is associated with significant systemic toxicity. In the realm of combination therapy, metformin, a biguanide drug conventionally used as a first-line treatment for type ۲ diabetes, has recently emerged as a valuable adjunct in the treatment of a diverse spectrum of tumors. This study aimed to elucidate the impact of metformin on sensitizing the human cerebral GBM cancer cell line (AMGM) to cisplatin chemotherapy by employing the comet assay as a means to assess DNA damage, thereby advocating the potential of metformin as an adjuvant for cisplatin-based therapy.Method: In this experimental study, the AMGM cell line was cultured and subsequently treated with either single-agent cisplatin, metformin, or a combination of both drugs. Cell viability was assessed through growth inhibition calculations. The Chou–Talalay analysis was used to assess the cooperative effect of this drug combination. Furthermore, DNA fragmentation was quantified using the alkaline comet assay technique.Results: The findings demonstrate that metformin significantly potentiates the therapeutic efficacy of cisplatin by synergistically inhibiting the growth of AMGM cells and reducing DNA damage.Conclusion: These results underscore the potential utility of metformin as a valuable adjunct in enhancing the clinical effectiveness of chemotherapy regimens.

کلیدواژه ها:

Metformin ، Cisplatin ، Glioblastoma ، Synergism effect ، DNA fragmentation