XRCC2 promotes colorectal cancer cell growth, regulates cell cycle progression, and apoptosis.
XRCC2 promotes colorectal cancer cell growth, regulates cell cycle progression, and apoptosis.
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DOI：
10.1097/md.0000000000000294
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发表时间：
2014-12
期刊：
影响因子：
1.6
通讯作者：
Zhan W
中科院分区：
文献类型：
--
作者：
Xu K;Song X;Chen Z;Qin C;He Y;Zhan W
补充数字内容可在文本中获得X射线修复补充缺陷修复在中国仓鼠细胞2（XRCC 2）和聚（ADP-核糖）聚合酶1（PARP 1）都发挥重要作用同源重组DNA修复。根据合成致死理论，与表达XRCC 2的细胞相比，XRCC 2缺陷细胞对PARP 1抑制剂更敏感。我们研究了XRCC 2在结直肠癌（CRC）中的表达和功能，以及不同XRCC 2水平的CRC细胞对PARP 1抑制剂的敏感性特征。我们在这项研究中纳入了153例接受手术的CRC患者。使用免疫组织化学评估XRCC 2表达。构建具有低或高XRCC 2表达的稳定CRC SW 480细胞系。在用PARP 1抑制剂奥拉帕尼处理后，测定具有不同XRCC 2水平的细胞的活力;使用流式细胞术分析细胞周期分布和凋亡。Western blotting检测B细胞淋巴瘤2（Bcl-2）蛋白表达。XRCC 2在原发结直肠癌组织中的阳性表达率显著高于癌旁正常组织，且XRCC 2的表达与肿瘤部位、Dukes分期、TNM分期有关。XRCC 2过表达可抑制结直肠癌细胞凋亡，并通过使细胞富集于G 0/G1期而促进增殖。此外，奥拉帕尼抑制增殖，并且奥拉帕尼在具有高XRCC 2表达的CRC细胞中的敏感性更高。XRCC 2高表达促进CRC细胞增殖并使细胞富集在G 0/G1期，但抑制凋亡。高XRCC 2表达细胞对奥拉帕尼更敏感，奥拉帕尼抑制其活力。
Supplemental Digital Content is available in the text X-ray repair complementing defective repair in Chinese hamster cells 2 (XRCC2) and poly(ADP-ribose) polymerase 1 (PARP1) both play important roles in homologous recombination DNA repair. According to the theory of synthetic lethality, XRCC2-deficient cells are more sensitive to PARP1 inhibitors compared to XRCC2-expressing cells. We investigated XRCC2 expression and function in colorectal cancer (CRC), and the characteristics of sensitivity to PARP1 inhibitor in CRC cells with different XRCC2 levels. We enrolled 153 patients with CRC who had undergone surgery in this study. XRCC2 expression was assessed using immunohistochemistry. Stable CRC SW480 cell lines with low or high XRCC2 expression were constructed. Following treatment with the PARP1 inhibitor olaparib, the viability of cells with different XRCC2 levels was determined; cell cycle distribution and apoptosis were analyzed using flow cytometry. B-cell lymphoma-2 (Bcl-2) protein expression was measured by Western blotting. The positive rates of XRCC2 in primary CRC tissue were significantly higher than that in the matched adjacent noncancerous tissue, and XRCC2 expression status in primary CRC was related to tumor site, Dukes’ stage, and tumor-nodes-metastasis (TNM) stage. XRCC2 overexpression inhibited CRC cell apoptosis and promoted proliferation by enriching cells in the G0/G1 phase. Moreover, olaparib suppressed proliferation, and olaparib sensitivity in CRC cells with high XRCC2 expression was greater. High XRCC2 expression promotes CRC cell proliferation and enriches cells in the G0/G1 phase but inhibits apoptosis. High XRCC2 expression cells are more sensitive to olaparib, which inhibits their viability.