XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer
XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer
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XRCC2 缺陷细胞在结直肠癌中对 5-氟尿嘧啶高度敏感
DOI：
10.1159/000481762
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Qin CJ
中科院分区：
文献类型：
--
作者：
Zhang YZ;An JH;Liu YX;Wu XC;Han SS;Ren XQ;Qin CJ
背景/目的：抑制5-氟尿嘧啶（5-FU）诱导的DNA损伤的修复可能会改善肿瘤对抗癌药物的反应。XRCC 2是DNA修复的关键因子。然而，XRCC 2在用5-FU治疗的结肠直肠癌（CRC）的化学抗性中的作用仍不清楚。本研究旨在探讨XRCC 2表达是否影响结直肠癌的化疗敏感性。方法：检测XRCC 2在结直肠癌组织中的表达，分析其临床意义。用CCK-8法检测XRCC 2对大肠癌细胞增殖的影响，流式细胞术检测XRCC 2对大肠癌细胞周期分布和凋亡的影响，γ H2 AX灶形成实验检测5-FU对大肠癌细胞DNA双链断裂修复的影响。结果如下：XRCC 2在结直肠癌组织中的表达显著高于正常组织，且XRCC 2的表达与结直肠癌的T分期、M分期、TNM分期、杜克分期、肝转移和淋巴结转移密切相关。XRCC 2表达可能是判断大肠癌患者预后的独立指标。XRCC 2阴性表达的患者对5-FU化疗的敏感性高于XRCC 2阳性表达的患者。此外，我们的观察显示，敲低CRC细胞中的XRCC 2增加了细胞增殖、凋亡和细胞周期停滞方面对5-FU的敏感性。DNA DSB修复在XRCC 2缺陷型细胞中比在XRCC 2野生型细胞中慢。结论：我们的研究表明，XRCC 2可能在CRC中发挥重要作用，并作为一种新的预后指标，XRCC 2的下调可能有助于在5-FU化疗期间使CRC细胞增敏。
Background/Aims: Inhibition of the repair of 5-fluorouracil (5-FU)-induced DNA lesions may improve the responses of tumors to anticancer agents. XRCC2 is a key factor in DNA repair. However, the role of XRCC2 in the chemoresistance of colorectal cancer (CRC) treated with 5-FU remains unclear. The aim of this study is to investigate whether XRCC2 expression affects the chemosensitivity of colorectal cancer. Methods: XRCC2 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of XRCC2 expression. Following treatment with 5-FU, the effect of XRCC2 on proliferation was evaluated via a CCK-8 assay, the effects on cell cycle distribution and apoptosis were analyzed using flow cytometry, and γH2AX foci formation assays were performed to examine the influence of 5-FU on DNA Double-strand breaks(DSBs) repair in CRC cells. Results: XRCC2 expression in CRC tissues was significantly higher than that in normal tissues, and this increased XRCC2 expression was associated with advanced T staging, M staging, TNM staging, Duke’s staging, and greater liver and lymph node metastases. XRCC2 expression might be an independent prognostic indicator for CRC patients. Patients with negative XRCC2 expression exhibit greater sensitivity to treatment with 5-FU-based chemotherapy than those with positive XRCC2 expression. Moreover, our observations revealed that the knockdown of XRCC2 in CRC cells increased the sensitivities to 5-FU in terms of cell proliferation, apoptosis and cell cycle arrest. DNA DSBs repair was slower in the XRCC2-deficient cells than in the XRCC2-wild type cells. Conclusion: Our study demonstrated that XRCC2 might play an important role in CRC and function as a novel prognostic indicator and that the down-regulation of XRCC2 may be useful for sensitizing CRC cells during 5-FU chemotherapy.
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影响因子：
1.6
作者：
Xu K;Song X;Chen Z;Qin C;He Y;Zhan W
通讯作者：
Zhan W
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影响因子：
5.6
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
通讯作者：
Liu Q
影响因子：
9
作者：
通讯作者：
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影响因子：
11.5
作者：
Lorat, Yvonne;Schanz, Stefanie;Ruebe, Claudia E.
通讯作者：
Ruebe, Claudia E.
影响因子：
45.3
作者：
Spigel, David R.;Greco, F. Anthony;Hainsworth, John D.
通讯作者：
Hainsworth, John D.