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Article

shRNA-Mediated XRCC2 Gene Knockdown Efficiently Sensitizes Colon Tumor Cells to X-ray Irradiation in Vitro and in Vivo

by
Qin Wang
1,
Yan Wang
1,
Liqing Du
1,
Chang Xu
1,
Yuanming Sun
1,
Bing Yang
2,
Zhijuan Sun
1,
Yue Fu
1,
Lu Cai
3,
Saijun Fan
1,
Feiyue Fan
1,* and
Qiang Liu
1,*
1
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
2
Department of Cell Biology, Tianjin Medical University, Tianjin 300070, China
3
Department of Pediatrics of University of Louisville, Louisville, KY 40202, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2014, 15(2), 2157-2171; https://doi.org/10.3390/ijms15022157
Submission received: 18 November 2013 / Revised: 30 December 2013 / Accepted: 16 January 2014 / Published: 29 January 2014
(This article belongs to the Collection Radiation Toxicity in Cells)
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Abstract

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.
Keywords: XRCC2; RNA interference; colon cancer; ionizing radiation; radiosensitivity XRCC2; RNA interference; colon cancer; ionizing radiation; radiosensitivity
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MDPI and ACS Style

Wang, Q.; Wang, Y.; Du, L.; Xu, C.; Sun, Y.; Yang, B.; Sun, Z.; Fu, Y.; Cai, L.; Fan, S.; et al. shRNA-Mediated XRCC2 Gene Knockdown Efficiently Sensitizes Colon Tumor Cells to X-ray Irradiation in Vitro and in Vivo . Int. J. Mol. Sci. 2014, 15, 2157-2171. https://doi.org/10.3390/ijms15022157

AMA Style

Wang Q, Wang Y, Du L, Xu C, Sun Y, Yang B, Sun Z, Fu Y, Cai L, Fan S, et al. shRNA-Mediated XRCC2 Gene Knockdown Efficiently Sensitizes Colon Tumor Cells to X-ray Irradiation in Vitro and in Vivo . International Journal of Molecular Sciences. 2014; 15(2):2157-2171. https://doi.org/10.3390/ijms15022157

Chicago/Turabian Style

Wang, Qin, Yan Wang, Liqing Du, Chang Xu, Yuanming Sun, Bing Yang, Zhijuan Sun, Yue Fu, Lu Cai, Saijun Fan, and et al. 2014. "shRNA-Mediated XRCC2 Gene Knockdown Efficiently Sensitizes Colon Tumor Cells to X-ray Irradiation in Vitro and in Vivo " International Journal of Molecular Sciences 15, no. 2: 2157-2171. https://doi.org/10.3390/ijms15022157

APA Style

Wang, Q., Wang, Y., Du, L., Xu, C., Sun, Y., Yang, B., Sun, Z., Fu, Y., Cai, L., Fan, S., Fan, F., & Liu, Q. (2014). shRNA-Mediated XRCC2 Gene Knockdown Efficiently Sensitizes Colon Tumor Cells to X-ray Irradiation in Vitro and in Vivo . International Journal of Molecular Sciences, 15(2), 2157-2171. https://doi.org/10.3390/ijms15022157

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