Overexpression of xeroderma pigmentosum group C decreases the chemotherapeutic sensitivity of colorectal carcinoma cells to cisplatin

Zhang,Yi; Cao,Jia; Meng,Yanni; Qu,Chunying; Shen,Feng; Xu,Leiming

doi:10.3892/ol.2018.8127

Overexpression of xeroderma pigmentosum group C decreases the chemotherapeutic sensitivity of colorectal carcinoma cells to cisplatin

Authors:
- Yi Zhang
- Jia Cao
- Yanni Meng
- Chunying Qu
- Feng Shen
- Leiming Xu
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Affiliations: Department of Digestive Endoscopic Diagnosis and Treatment, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P.R. China
Published online on: February 27, 2018 https://doi.org/10.3892/ol.2018.8127
Pages: 6336-6344
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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. In vitro, 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. In vivo, 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.

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