Metformin enhances the radiosensitizing effect of cisplatin in non-small cell lung cancer cell lines with different cisplatin sensitivities

摘要: Cisplatin is an extensively used chemotherapeutic drug for lung cancer, but the development of resistance decreases its effectiveness in treatments non-small cell cancer (NSCLC). In this study, we examined effects metformin, a widely antidiabetic drug, on cisplatin radiosensitization NSCLC lines. Human lines, A549 (cisplatin-resistant) and H460 (cisplatin-sensitive), were treated with or combination both drugs before ionizing radiation. Cell proliferation, clonogenic assays, western blotting, cisplatin-DNA adduct formation immunocytochemistry to characterize effects. Metformin increased radiosensitivity cells. showed additive over-additive radiation response assay lines (p = 0.018 interaction effect between metformin), respectively. At molecular level, metformin led significant increase compared alone (p < 0.01, ANOVA-F test). This was accompanied by decreased expression excision repair cross-complementation 1 (ERCC1), key enzyme nucleotide pathway. Furthermore, each treatment yielded lowest level radiation-induced Rad51 foci, essential protein homologous recombination repair. Ionizing γ-H2AX 53BP1 foci persisted longer presence metformin. Pharmacological inhibition AMP-activated kinase (AMPK) demonstrated that enhances radiosensitizing through AMPK-dependent pathway only not Our results suggest can enhance combined radiotherapy sensitize these cells are sensitized alone.