shRNA-mediated XRCC2 gene knockdown efficiently sensitizes colon tumor cells to X-ray irradiation in vitro and in vivo.
shRNA-mediated XRCC2 gene knockdown efficiently sensitizes colon tumor cells to X-ray irradiation in vitro and in vivo.
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shRNA 介导的 XRCC2 基因敲低可有效提高结肠肿瘤细胞对体外和体内 X 射线照射的敏感性
DOI：
10.3390/ijms15022157
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发表时间：
2014-01-29
影响因子：
5.6
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Wang Q;Wang Y;Du L;Xu C;Sun Y;Yang B;Sun Z;Fu Y;Cai L;Fan S;Fan F;Liu Q
结肠癌是消化道最常见的肿瘤之一。对电离辐射（IR）的抵抗降低了这些患者放疗的疗效。XRCC 2是DNA同源重组修复的关键蛋白，其高表达与增强对IR诱导的DNA损伤的抵抗力有关。体外培养结肠肿瘤细胞（T84细胞系），并将源自该细胞系的肿瘤作为裸鼠异种移植物增殖。通过在T84细胞中使用基于载体的短发夹RNA（shRNA）来抑制XRCC 2的表达。我们发现XRCC 2基因的表达下调能有效抑制X射线诱导的T84细胞增殖和集落形成，并导致细胞凋亡和细胞周期阻滞于G2/M期。此外，肿瘤异种移植研究表明，XRCC 2沉默抑制体内放射治疗后的致瘤性。我们的数据表明，抑制XRCC 2表达使结肠肿瘤细胞在体外和体内对放射治疗更敏感，这意味着XRCC 2作为一个有前途的治疗靶点，用于治疗放射抗性的人结肠癌。
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.
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影响因子：
3.4
作者：
Rajesh, Changanamkandath;Gruver, Aaron M.;Pittman, Douglas L.
通讯作者：
Pittman, Douglas L.
影响因子：
11.2
作者：
Zheng, Zhiming;Ng, Wooi Loon;Wang, Ya
通讯作者：
Wang, Ya
XRCC2中的遗传变异：对结直肠癌肿瘤发生的新见解。
DOI：
10.1158/1055-9965.epi-09-0187
发表时间：
2009-09
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Curtin K;Lin WY;George R;Katory M;Shorto J;Cannon-Albright LA;Smith G;Bishop DT;Cox A;Camp NJ;Colorectal Cancer Study Group
通讯作者：
Colorectal Cancer Study Group
影响因子：
5.2
作者：
Haines, Jackie W.;Coster, Margaret R.;Bouffler, Simon D.
通讯作者：
Bouffler, Simon D.
影响因子：
4.7
作者：
Liu, Yanhong;Shete, Sanjay;Bondy, Melissa L.
通讯作者：
Bondy, Melissa L.