RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer.

Chao Xiao, Yupeng Wang, Miao Zheng, Jian Chen, Guohe Song, Zhijie Zhou, Chongzhi Zhou, Xing Sun, Lin Zhong, Erxun Ding, Yi Zhang, Liu Yang, Gang Wu, Shifeng Xu, Hong Zhang, Xiaoliang Wang

Cancer science 2018 Apr

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Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. The present study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. After SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and protein increased over time in both cells. Moreover, a significant reduction in clonogenic survival and a decrease in cell viability in parallel with an obvious increase in cell apoptosis were demonstrated in irradiated RBBP6-knockdown cells. Transfection with RBBP6 shRNA improved the levels of G2-M phase arrest, which blocked the cells in a more radiosensitive period of the cell cycle. These observations indicated that cell cycle and apoptosis mechanisms may be connected with tumor cell survival following radiotherapy. In vivo, the tumor growth rate of nude mice in the RBBP6-knockdown group was significantly slower than that in other groups. These results indicated that RBBP6 overexpression could resist colorectal cancer cells against radiation by regulating cell cycle and apoptosis pathways, and inhibition of RBBP6 could enhance radiosensitivity of human colorectal cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Citation

Chao Xiao, Yupeng Wang, Miao Zheng, Jian Chen, Guohe Song, Zhijie Zhou, Chongzhi Zhou, Xing Sun, Lin Zhong, Erxun Ding, Yi Zhang, Liu Yang, Gang Wu, Shifeng Xu, Hong Zhang, Xiaoliang Wang. RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer. Cancer science. 2018 Apr;109(4):1075-1087