Gene Expression and Pathway Analysis of Radiation-Induced Apoptosis in C-4 I Cervical Cancer Cells

Abstract

Objective: The present study aimed to determine whether a single-fraction of gamma radiation could induce the expression of specifc genes involved in apoptosis signaling pathways, which helps us in better understanding cancer dynamics and treatment targets for cancer. Materials and methods: C-4 I cells were treated with a single fraction of gamma radiation at various doses (0, 2, 8, 16, 32 and 64 Gy) and investigated after incubation for fve time periods (0, 24, 48, 60 and 72 h). The proliferation of C-4 I cells was measured by MTT assay, but apoptotic index (AI) and apoptotic morphological features were assessed by fluorescent microscopy. Moreover, the expression of the apoptotic genes was evaluated using microarray and qRT-PCR molecular processes. In addition, gene ontology and pathway analysis were performed. Results: Gamma irradiation inhibits proliferation of C-4 I cells in a dose- and timedependent manner, and 16 Gy was identifed as the IC50 and AI dose. Microarray and qRT-PCR results monitored the expression of some factors that are known apoptosis activators were up regulated by gamma radiation treatment, whereas some anti-apoptosis members were down regulated. Pathway analysis identifed that signifcant pathways related to apoptosis, cell cycle and P53 were signifcantly enriched. Conclusions: These results provide evidence that gamma radiation directly induces antiproliferative effects by altering the expression of genes associated with cell proliferation and apoptosis pathways in C-4 I cells.