shRNA-mediated XRCC2 gene knockdown efficiently sensitizes colon tumor cells to X-ray irradiation in vitro and in vivo.
Colon cancer is one of the most common tumors of the digestive tract. Resistance to ionizing radiation (IR) decreased therapeutic efficiency in these patients' radiotherapy. XRCC2 is the key protein of DNA homologous recombination repair, and its high expression is associated with enhanced resistance to DNA damage induced by IR. Here, we investigated the effect of XRCC2 silencing on colon tumor cells' growth and sensitivity to X-radiation in vitro and in vivo. Colon tumor cells (T84 cell line) were cultivated in vitro and tumors originated from the cell line were propagated as xenografts in nude mice. The suppression of XRCC2 expression was achieved by using vector-based short hairpin RNA (shRNA) in T84 cells. We found that the knockdown of XRCC2 expression effectively decreased T84 cellular proliferation and colony formation, and led to cell apoptosis and cell cycle arrested in G2/M phase induced by X-radiation in vitro. In addition, tumor xenograft studies suggested that XRCC2 silencing inhibited tumorigenicity after radiation treatment in vivo. Our data suggest that the suppression of XRCC2 expression rendered colon tumor cells more sensitive to radiation therapy in vitro and in vivo, implying XRCC2 as a promising therapeutic target for the treatment of radioresistant human colon cancer.
Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. wangqin@irm-cams.ac.cn.
Qin
Q
Wang
Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. wangyan@irm-cams.ac.cn.
Yan
Y
Wang
Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. dlq@irm-cams.ac.cn.
Liqing
L
Du
Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. xuchang@irm-cams.ac.cn.
Chang
C
Xu
Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. sunyuanming@irm-cams.ac.cn.
Yuanming
Y
Sun
Department of Cell Biology, Tianjin Medical University, Tianjin 300070, China. yangbingtj@aol.com.
Bing
B
Yang
Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. sunzj@irm-cams.ac.cn.
Zhijuan
Z
Sun
Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. wddr0710@gmail.com.
Yue
Y
Fu
Department of Pediatrics of University of Louisville, Louisville, KY 40202, USA. lu.cai@louisville.edu.
Lu
L
Cai
Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. fansaijun@irm-cams.ac.cn.
Saijun
S
Fan
Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. fanfeiyue@irm-cams.ac.cn.
Feiyue
F
Fan
Tianjin Key Lab of Molecular Nuclear Medicine, Institute of Radiation Medicine of Chinese, Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China. liuqiang@irm-cams.ac.cn.
Qiang
Q
Liu
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D047368:Tumor Burden; D014965:X-Rays
D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C113187:XRCC2 protein, human