Abstract A1: MicroRNAs expression profile associated with radioresistance in lung cancer

Abstract

Abstract Lung cancer is the neoplasia with highest incidence and mortality worldwide. One of the strategies of treatment for this tumor type is based on ionizing radiation. Radiation induces cytotoxicity through some mechanisms, including gene expression changes. Recently, microRNAs (miRNAs) have been described as one of the molecules that regulate expression genes and may contributes to radioresistance in several tumor types. Global miRNAs expression profiles of radiosensitive and radioresistant lung tumor cells may elucidate the molecular mechanism related to tumoral radioresistance. In order to identify miRNAs associated with innate and acquired radioresistance, we will evaluate the miRNAs expression profiles in two lung carcinoma cell lines and in the same cell lines with acquire radioresistance by fractionated doses radiation treatment. For establish the median lethal dose radiation, H1944 and Calu-1 lung carcinoma cell lines were treated with increasing doses of X-rays (from 2 to 12 Gy). Cell survival, proliferative ability and clonogenic potential postradiation were evaluated. Moreover, we will generate a model of acquired radioresistance by treating lung tumor cells with fractionated doses of 2 Gy X-rays up to total dose of 60 Gy for to evaluate the expression of miRNAs in cells with acquired radioresistance. Results showed differential sensitivity to radiotherapy from lung tumors cells, whit 8 Gy as median lethal dose radiation. For to evaluate the expression of miRNAs during innate response to radiotherapy, total RNA was obtained from tumor cells treated with 8 Gy of X-rays. Additionally, it has been obtained lung tumor cells clones with treatment total doses of 28 Gy in a fractionated radiation scheme. These results will allow compare miRNAs expression during immediate cell response to radiation and those whose expression will modified during fractionated radiation treatment and may be associated with radioresistance acquired, which contribute to understanding the molecular mechanism to radioresistance in lung cancer.