Inhibitory effect of obatoclax mesylate-Loaded nanoparticles on lung cancer through Bcl-2 pathway

Abstract

Lung cancer is a common tumor with poor survival, despite great advancements in etiology and treatments for lung cancer in recent years. Nanoparticles (NPs) are highlighted as a promising tool for drug treatment to improve patients’ outcomes. Obatoclax mesylate (OM) is a current experimental drug for treatment of cancers, and modified OM is expected to more effectively control progression of diseases. Our study assessed the efficacy of combined NPs and OM on tumors. After synthesis of OM-NPs and examination of their characteristics, we treated lung cancer cells with synthesized OM-NPs and OM, respectively. Besides, animal model of lung cancer was established to explore the impact of modified OM on tumor growth. Cytotoxicity of the NPs and their inhibitory effect on tumor cells was assessed. Administration of OM-NPs effectively downregulated Bcl-2 and Bcl-xl, upregulated Bax, Cyto-c, cleavage of Caspase-9, Caspase-3 and poly ADP-ribose polymerase (PARP.) modified with NPs, the OM exerted greater inhibitory effect on lung cancer cell proliferation, and significantly induced apoptosis, prolonged circulation time for NPs and improved targeted ability. The OM-NPs prepared in this study effectively reduced lung cancer cells proliferation and inhibited tumor growth. These findings indicate the potential of NPs on targeted therapy.