Zhang Yi, Cao Jia, Meng Yanni, Qu Chunying, Shen Feng, Xu Leiming
Department of Digestive Endoscopic Diagnosis and Treatment, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P.R. China.
Oncol Lett. 2018 May;15(5):6336-6344. doi: 10.3892/ol.2018.8127. Epub 2018 Feb 27.
Xeroderma pigmentosum group C (XPC) is a DNA-damage-recognition gene active at the early stage of DNA repair. XPC also participates in regulation of cell-cycle checkpoint and DNA-damage-induced apoptosis. In the present study, the expression levels of genes involved in nucleotide excision repair (NER) were assessed in human colorectal cancer (CRC) tissue. This analysis revealed that expression of XPC mRNA significantly increased in colorectal carcinoma tissues compared with matched normal controls. Expression of XPC gradually increased along with the degree of progression of CRC. , an XTT assay demonstrated that small interfering RNA (siRNA) targeting XPC significantly increased the sensitivity of CRC SW480 cells to cisplatin, whereas cells transfected with a XPC-overexpression plasmid became more resistant to cisplatin. Furthermore, flow cytometry revealed that the proportion of apoptotic cells significantly increased in XPC-knockdown cells upon cisplatin treatment. However, the overexpression XPC significantly increased the resistance of cells to cisplatin. , tumor growth was significantly reduced in tumor-bearing mice when the XPC gene was knocked down. Upregulation of the expression of pro-apoptotic Bcl-associated X and downregulation of the anti-apoptotic B-cell lymphoma 2 proteins was observed in the implanted tumor tissue. In conclusion, XPC serves a key role in chemotherapeutic sensitivity of CRC to cisplatin, meaning that it may be a potential target for chemotherapy of CRC.
着色性干皮病C组（XPC）是一种在DNA修复早期具有活性的DNA损伤识别基因。XPC还参与细胞周期检查点的调控以及DNA损伤诱导的细胞凋亡。在本研究中，评估了人类结直肠癌（CRC）组织中参与核苷酸切除修复（NER）的基因的表达水平。该分析显示，与匹配的正常对照相比，结直肠癌组织中XPC mRNA的表达显著增加。XPC的表达随着CRC进展程度的增加而逐渐升高。此外，XTT检测表明，靶向XPC的小干扰RNA（siRNA）显著增加了CRC SW480细胞对顺铂的敏感性，而转染了XPC过表达质粒的细胞对顺铂的抗性增强。此外，流式细胞术显示，顺铂处理后，XPC敲低的细胞中凋亡细胞的比例显著增加。然而，XPC的过表达显著增加了细胞对顺铂的抗性。另外，当XPC基因被敲低时，荷瘤小鼠的肿瘤生长显著降低。在植入的肿瘤组织中观察到促凋亡的Bcl相关X蛋白表达上调，抗凋亡的B细胞淋巴瘤2蛋白表达下调。总之，XPC在CRC对顺铂的化疗敏感性中起关键作用，这意味着它可能是CRC化疗的一个潜在靶点。
