RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer.
RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer.
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RBBP6 增加放射抗性并可作为结直肠癌术前放疗的治疗靶点
DOI：
10.1111/cas.13516
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发表时间：
2018-04
期刊：
影响因子：
5.7
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Xiao C;Wang Y;Zheng M;Chen J;Song G;Zhou Z;Zhou C;Sun X;Zhong L;Ding E;Zhang Y;Yang L;Wu G;Xu S;Zhang H;Wang X
放射治疗(RT)可以作为一种术前治疗，以降低最初不能切除的局部直肠癌的分期，但放射抵抗和复发仍然是一个重要的问题。视网膜母细胞瘤结合蛋白6(RBBP6)在体内和体外均参与细胞周期、细胞凋亡和化疗耐药的调节。本研究探讨了抑制RBBP6的表达是否会提高人结直肠癌细胞的放射敏感性。SW620和HT29细胞受辐射后，RBBP6mRNA和蛋白水平均随时间延长而升高。此外，在照射后的RBBP6基因敲除细胞中，克隆存活率显著降低，细胞存活率下降，同时细胞凋亡率明显增加。转染人RBBP6 shRNA可使细胞发生G2-M期阻滞，使细胞处于辐射敏感期。这些观察表明，细胞周期和细胞凋亡机制可能与肿瘤细胞放疗后的生存有关。在体内，RBBP6基因敲除组裸鼠的肿瘤生长速度明显慢于其他组。这些结果表明，RBBP6过表达可通过调节细胞周期和细胞凋亡途径来抵抗放射治疗，抑制RBBP6可增强人结直肠癌细胞的放射敏感性。
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.
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影响因子：
4.3
作者：
Garg PK;Sharma J;Jakhetiya A;Goel A;Gaur MK
通讯作者：
Gaur MK
影响因子：
4
作者：
Moela P;Motadi LR
通讯作者：
Motadi LR
影响因子：
9.2
作者：
Li Y;Wang J;Ma X;Tan L;Yan Y;Xue C;Hui B;Liu R;Ma H;Ren J
通讯作者：
Ren J
影响因子：
3.3
作者：
Deng, Qian;Huang, Chun-mei;Wang, Wei
通讯作者：
Wang, Wei
结直肠癌是美国 50 岁以下成年人癌症发病率和死亡率的主要原因：一项基于 SEER 的分析，与其他年轻发病的癌症进行比较。
DOI：
10.1136/jim-2016-000229
发表时间：
2017-03
期刊：
Journal of investigative medicine : the official publication of the American Federation for Clinical Research
影响因子：
--
作者：
Bhandari A;Woodhouse M;Gupta S
通讯作者：
Gupta S