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

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.