Abstract 1043: Autophagy induces cytoprotection in cisplatin-treated lung cancer cells

Abstract

Abstract Purpose: Most of lung cancer patients had received the systemic chemotherapy because they had diagnosed the advanced stage at presentation. Cislplatin-based chemotherapy is main regimen for advanced lung cancer. But serious adverse reaction (SAE) had occurred after chemotherapy. This is main reason for chemotherapy withdrawal. If we will use the reduced dose of cispaltin, cisplatin-based the chemotheray will be continued. To figure out whether the effect of low dose of cisplatin will be synergistically enhance by autophagy inhibiton, even though the reduced dose of cisplatin less effect for treatment response, We investigated that role of autophagy by 3-methyladenine, class III PI3kinase inhibitor in cisplatin-treated lung cancer cells. Methods: Lung cancer cells were incubated with normal media and treated the 5uM (LD20) and 20uM(LD50) of cislpaltin according to time dependent. We examined the sensitivity to low or high doses of cisplatin treatment using the MTT cell viability assay and compared apoptosis and autophagy by nuclear stianing, apoptotic or autophagic related proteins or autophagic vacuoles. autophagy is also displayed the development of acidic vascular organelles by acridine orange and the fluorescent expression of GFP-LC3 protein in the GFP-LC3 transfected cells. Result: Low dose of cisplatin-treated lung cancer cells is relatively less sensitive to cell death rather than high dose treated cells in a time-dependent manners. We didnot find out the nuclear fragmentation in lower dose even though detected its in high dose. PARP cleavages also were not detected in low dose of cisplatin exception 24H. We observed that massive vacuolization in the cytoplasm were seen at lower dose treated cells. Acridine orange stain-positive cells also were increased according to time dependent. We figured out that the autophagosome-incorporated LC3 II protein expression more increased in low dose treated cells (24H to 48H) in spite of no detection of LC3 II in high dose treated cells. The expression of GFP-LC3 were increased in 5uM treated cells by time-dependent manner. When 3-methyladenine, class III PI3kinase inhibitor, was pretreated in 5uM cisplatin-treated lung cancer cells, cell survival significantly were decreased. Conclusion: Autophagy induces cytoprotection in lower dose of cisplatin-treated lung cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1043.