Induction of Apoptosis Pathways in Human Cervical Carcinoma Cells by ionizing Radiation

Abstract

More than half of all cancer patients receiving radiotherapy during the course of treatment, and it is the most effective therapy for cervical cancer in advanced stages. The objectives of this study are to identify changes in gene expression, which involved in apoptosis pathways induced by gamma radiation, these identified genes and gene-related signalling pathways may provide meaningful biomarkers for understanding cancer dynamics and treatment targets against human cervical cancer. Cervical cancer cells were exposed to various doses of a single fraction of gamma radiation. After incubation for different periods, the proliferation of C-4 I and HeLa cells were investigated by MTT assay, wile morphological features were assessed by fluorescent microscopy to measure the Apoptotic Index (AI). In addition, gene expression was evaluated using micro-array molecular processes, and signalling pathway analysis were performed. Gamma irradiation inhibits proliferation of HeLa and C-4 I cells in a time- and dose- dependent manner. From our results a significant difference was observed between HeLa and C-4 I cell lines (p < 0.01), whereas, HeLa cells seemed to be radio resistant, while C-4 I cells radiosensitive. IC50 and AI dose for C-4 I and HeLa cells were 16 Gy and 32 Gy respectively. Microarray results monitored the expression of some factors that are known apoptosis activators were up regulated by gamma radiation treatment, whereas some antiapoptosis members were down regulated. Pathway analysis identified that significant pathways related to apoptosis, WNT, cell cycle and P53 were significantly reinforced. These results give evidence that ionized radiation directly induces anti proliferative effects by converting the expression of genes related to apoptosis and cell proliferation pathways in HeLa and C-4 I cervical cancer cells. Identification of specific genes may be beneficial in novel treatment strategy to increase the cancer cell sensitivity to radiotherapy by modulation of many genes expression. Our study is a kind of screening rather than detailed research. We need further investigation to define these identified genes in vitro and in vivo.