RT Journal Article
SR Electronic
T1 Oxaliplatin Regulates DNA Repair Responding to Ionizing Radiation and Enhances Radiosensitivity of Human Cervical Cancer Cells
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP 782-786
OP 782-786
DO 10.1111/IGC.0b013e3181a44618
VO 19
IS 4
A1 Yang, Yuh-Cheng
A1 Chao, K.S. Clifford
A1 Lin, Chin-Ping
A1 Chen, Yu-Yawn
A1 Wang, Kung-Liahng
A1 Chen, Yu-Jen
YR 2009
UL http://ijgc.bmj.com/content/19/4/782-786.abstract
AB Concurrent chemoradiotherapy is a standard treatment of locally advanced cervical carcinoma. The most widely used drug for chemoirradiation is cisplatin. However, its toxicity and drug resistance remain major concerns in clinical practice. This study was designed to evaluate the effect of oxaliplatin, another platinum compound, on enhancing radiosensitivity in cervical cancer cell lines. Human HeLa and SiHa cells were used. Cell survival after irradiation with or without oxaliplatin pretreatment was assessed by performing colony-formation assays. Sensitizer enhancement ratios were calculated using a linear quadratic model. Cell morphology was observed after staining with Wright dye. To evaluate the machinery to repair DNA damage, cellular protein was subjected to Western blotting to assess the expression of damage-related molecules. Nontoxic doses of oxaliplatin were 5 and 10 μmol/L for HeLa and SiHa cells, respectively. Pretreatment with oxaliplatin markedly decreased, with a greater extent than cisplatin, the survival of irradiated HeLa cells. Maximal sensitizer enhancement ratios of oxaliplatin at 37% survival were 3.4 for HeLa cells and 4.8 for SiHa cells. Oxaliplatin pretreatment enhanced the cell cycle arrest in the G2/M phase and the radiation-induced mitotic catastrophe. Oxaliplatin modulated radiation-induced DNA double-strand breaks, as indicated by delayed abrogation of γ-H2AX, attenuation of radiation-induced phosphorylation of ataxia telangiectasia-mutated kinase and checkpoint kinase 2. In conclusion, oxaliplatin sensitized human HeLa and SiHa cells to ionizing radiation. This effect may involve modulation of ataxia telangiectasia-mutated kinase and checkpoint kinase 2 activation during DNA damage repair.Abbreviations: SERs - Sensitizer enhancement ratios, ATM - ataxia telangiectasia-mutated, Chk2 - checkpoint kinase 2, MTT - 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide