NBM-T-BMX-OS01, an Osthole Derivative, Sensitizes Human Lung Cancer A549 Cells to Cisplatin through AMPK-Dependent Inhibition of ERK and Akt Pathway.

摘要: Background: Drug combination therapies using cisplatin and natural products are common practice in the treatment of human lung cancer. Osthole is a compound extracted from number medicinal plants has been shown to exert strong anticancer activities with low toxicity. Methods: In present study, NBM-T-BMX-OS01 (BMX), derived semi-synthesis osthole, was evaluated treated A549 cells investigate its effect on resistance The BMX were measured by cell viablity‚ colony formation‚ TUNEL staining‚ flow cytometry cycle assay. fluorescence staining performed detect intracellular mitochondrial reactive oxygen species (ROS) generation. Western blot analysis, antagonists pretreatment small interfering RNA (siRNA) transfection used determine potential mechanism. Results: It found that, comparison single treatment, resulted greater efficacy inhibition proliferation formation, apoptosis induction arrest. results showed that due oxidative stress induced ROS addition, significantly attenuated phosphorylation ERK Akt, two important pro-survival kinases. contrast, inhibited activation AMPK, knockdown AMPK specific siRNA partially reversed BMX-induced as well synthetic effects activity cells. Conclusion: Taken together, this study provides might modulate through AMPK-ERK AMPK-Akt pathways. These also support role drug candidate for use