Verapamil (VER) Enhances the Cytotoxic Effects of Docetaxel and Vinblastine Combined Therapy Against Non-Small Cell Lung Cancer Cell Lines.

Abstract

Lung cancer is one of the foremost tumor-associated cause of death in the world. Most of the patients with NSCLC possesses an advanced disease at diagnosis, and are thus probable subject for systemic therapy. This study aims to evaluate the cytotoxicity of vinblastine and docetaxel combined therapy for the treatment of NSCLC, as well as verapamil (VER) enhancement of the combined therapy. We conducted P-glycoprotein (P-gp) gene expression, protein expression with RT-PCR and western blot respectively, apoptotic response of the combined therapy with VER is also determined using DAPI staining (%). Result of DAPI staining confirmed combination therapy promotes cell apoptosis to greater extent as compared to each drug alone. Real-time RT-PCR analysis revealed that mdr-1 expression level increased 6 fold with docetaxel (40 nM) and 2 fold with vinblastine (30 nM) after 24 h (p<0.001). Consequently, combination therapy reduced drug-induced up-regulation of mdr-1 significantly (p<0.05). VER with the drug combination increased P-gp expression (p<0.05). These data provide evidence showing combined therapy is a better approach to improve the efficacy of chemotherapy and decreasing drug resistance.