TY - JOUR 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 SP - 782-786 LP - 782-786 DO - 10.1111/IGC.0b013e3181a44618 VL - 19 IS - 4 AU - Yuh-Cheng Yang AU - K.S. Clifford Chao AU - Chin-Ping Lin AU - Yu-Yawn Chen AU - Kung-Liahng Wang AU - Yu-Jen Chen Y1 - 2009/04/01 UR - http://ijgc.bmj.com/content/19/4/782-786.abstract N2 - 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 ER -