Open AccessRBBP 6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer
Author(s) -
Xiao Chao,
Wang Yupeng,
Zheng Miao,
Chen Jian,
Song Guohe,
Zhou Zhijie,
Zhou Chongzhi,
Sun Xing,
Zhong Lin,
Ding Erxun,
Zhang Yi,
Yang Liu,
Wu Gang,
Xu Shifeng,
Zhang Hong,
Wang Xiaoliang
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13516
Subject(s) - radioresistance , radiosensitivity , cell cycle , colorectal cancer , apoptosis , cancer research , clonogenic assay , cell cycle checkpoint , gene knockdown , radiation therapy , cell growth , viability assay , cancer , cell , biology , in vivo , medicine , biochemistry , genetics , microbiology and biotechnology
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 ( RBBP 6) 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 RBBP 6 expression would improve radiosensitivity in human colorectal cancer cells. After SW 620 and HT 29 cells were exposed to radiation, the levels of RBBP 6 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 RBBP 6‐knockdown cells. Transfection with RBBP 6 sh RNA 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 RBBP 6‐knockdown group was significantly slower than that in other groups. These results indicated that RBBP 6 overexpression could resist colorectal cancer cells against radiation by regulating cell cycle and apoptosis pathways, and inhibition of RBBP 6 could enhance radiosensitivity of human colorectal cancer.