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Oxaliplatin Regulates DNA Repair Responding to Ionizing Radiation and Enhances Radiosensitivity of Human Cervical Cancer Cells
  1. Yuh-Cheng Yang*,,
  2. K.S. Clifford Chao,
  3. Chin-Ping Lin,
  4. Yu-Yawn Chen, MD§,
  5. Kung-Liahng Wang*, and
  6. Yu-Jen Chen, MD,
  1. *Departments of Gynecology and Obstetrics, and
  2. Departments of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan;
  3. Departments of Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX;
  4. §Departments of Department and Graduate School of Physical Education, National Taiwan College of Physical Education, Taichung;
  5. Departments of Mackay Medicine, Nursing, and Management College, Taipei; and
  6. Departments of Department of Radiation Oncology, Mackay Memorial Hospital, Taipei Taiwan.
  1. Address correspondence and reprint requests to Yu-Jen Chen, MD, Department of Radiation Oncology, Mackay Memorial Hospital, 92 Chung San N Rd, Section 2, Taipei 104, Taiwan. E-mail: chenmdphd{at} and Kung-Liahng Wang, MD, Department of Gynecology and Obstetrics, Mackay Memorial Hospital, 92 Chung San N Rd, Section 2, Taipei 104, Taiwan. E-mail: kl421229{at}


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

  • Oxaliplatin
  • Cervical cancer
  • Radiosensitization
  • DNA repair

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