Xialin Chen1,2, Rong Ji3, Jianjiang Liu2, Xueying Jin2, Hong Zhu4, Jianfang Wang5, Ming Chen6,7. 1. Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, NO.1055 Sanxiang Road, Suzhou, 215000, China. 2. Department of Radiation Oncology, Shaoxing People's Hospital, NO. 568, North Zhongxing Road, Shaoxing, 312000, China. 3. Department of Radiation Oncology, The Second Hospital of Shaoxing, Shaoxing, 312000, China. 4. Department of Radiation Oncology, Minhang Branch of Cancer Hospital of Fudan University, Shanghai, 200240, China. 5. Department of Radiation Oncology, Shaoxing People's Hospital, NO. 568, North Zhongxing Road, Shaoxing, 312000, China. sxwxdd@163.com. 6. Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, NO.1055 Sanxiang Road, Suzhou, 215000, China. chenming@zjcc.org.cn. 7. Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, 310000, China. chenming@zjcc.org.cn.
Abstract
BACKGROUND: Previous reports stated that DNA polymerase ζ is highly expressed in lung cancer tissues. The present study aimed to investigate the roles and underlying mechanism of DNA polymerase ζ in lung cancer cell radioresistance. METHODS: The A549 and HCC827 cells were used to evaluate the effects of different doses of radiation on the mRNA and protein expressions of DNA polymerase ζ. Multiple assays, including PCR, western blot, flow cytometry, and EdU have been used to investigate the roles of DNA polymerase ζ on the cellular behaviors of A549 and HCC827 cells. RESULTS: The mRNA and protein expression of REV7L in A549 and HCC827 cells were significantly increased after 6 Gy irradiation compared to the control group. In A549 and HCC827 cells, over-expression of polymerase ζ decreased the radiosensitivity, inhibited cell apoptosis as well as reduced oxidative stress; while the knockdown of polymerase ζ showed the opposite effects. Knockdown of Polymerase ζ in xenograft animal models significantly decreased tumor size and induced oxidative stress of tumor tissues after irradiation. DISCUSSION: Our results provided a theoretical basis for targeting DNA polymerase ζ to improve the radiosensitivity of the lung cancer cells to radiotherapy.
BACKGROUND: Previous reports stated that DNA polymerase ζ is highly expressed in lung cancer tissues. The present study aimed to investigate the roles and underlying mechanism of DNA polymerase ζ in lung cancer cell radioresistance. METHODS: The A549 and HCC827 cells were used to evaluate the effects of different doses of radiation on the mRNA and protein expressions of DNA polymerase ζ. Multiple assays, including PCR, western blot, flow cytometry, and EdU have been used to investigate the roles of DNA polymerase ζ on the cellular behaviors of A549 and HCC827 cells. RESULTS: The mRNA and protein expression of REV7L in A549 and HCC827 cells were significantly increased after 6 Gy irradiation compared to the control group. In A549 and HCC827 cells, over-expression of polymerase ζ decreased the radiosensitivity, inhibited cell apoptosis as well as reduced oxidative stress; while the knockdown of polymerase ζ showed the opposite effects. Knockdown of Polymerase ζ in xenograft animal models significantly decreased tumor size and induced oxidative stress of tumor tissues after irradiation. DISCUSSION: Our results provided a theoretical basis for targeting DNA polymerase ζ to improve the radiosensitivity of the lung cancer cells to radiotherapy.