The Role of SAPK/JNK Pathway in the Synergistic Effects of Metformin and Dacarbazine on Apoptosis in Raji and Ramos Lymphoma Cells

BACKGROUND: Besides the first-line medication for the treatment of type 2 diabetes, the growth inhibitory activity of metformin alone or in combination with conventional chemotherapeutics has been addressed on a panel of cell lines. In this study, we investigated the cytotoxicity and apoptosis of the metformin alone and in combination with dacarbazine in Raji and Ramos lymphoma cell lines. METHODS: Cell viability and apoptosis measured using resazurin assay, flow cytometry of PI stained cells and western blot analysis. RESULTS: Metformin showed synergistic cytotoxic effects in combination with dacarbazine, reduced cell viability, and increased apoptosis in Raji and Ramos lymphoma cells in comparison with the use of each drug alone. The activation of MAPK and SAPK/JNK (P-SAPK/JNK) were shown in both cells. CONCLUSION: Overall, the result verified the synergistic effect of the metformin-dacarbazine combination, which has the value in reducing the chemotherapeutic agent dose, adverse effect and the burden of treatment for the community and patients.