Vitamin C potentiates gefitinib-mediated tumor cell growth inhibition in human lung cancer cells (49.26)

Abstract

Abstract Malignancies of lung are the leading causes of cancer mortality in world wide and there are so many limitations in early detection of lung cancer, which eventually made the cancer detected at advanced stage. Conventional cytotoxic drugs have showed more increased response rate with grave toxicities. Recently, successful therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in lung cancer patients have been reported, although a mono-therapy still showed low response rate. Here, we investigated to elucidate whether the vitamin C has the adjuvant role as an antioxidant or other functions in EGFR tyrosine kinase inhibitor, gefitinib (Iressa ¢â), therapy in lung cancers. We used three kinds of human non-small cell lung cancer cell (NSCLC) lines depending on EGFR mutation, A549, Calu-3 and HCC827. A549 and Calu-3 are NSCLC cell lines which have wild type EGFR domain and showed relative resistance to gefitinib treatment. HCC827 is well known cell line of EGFR domain mutation. Vitamin C showed reduction of S phase in cell cycle and had function as an anti-oxidant. Also that could induce synergistic effects of EGFR tyrosine kinase inhibitor therapy in cellular proliferation and down-regulation of EGFR phosphorylation, AKT & ERK activation. Synergistic inhibitory effects of vitamin C with EGFR tyrosine kinase inhibitor therapy are showed in both wild and mutant EGFR cell lines. In this present study, we demonstrated an possible adjuvant role of vitamin C in EGFR tyrosine kinase inhibitor therapy in human NSCLC.