Increased expression of DNA repair gene XPF enhances resistance to hydroxycamptothecin in bladder cancer
Jie Li, Junlei Zhang, Yang Liu, Gang Ye
Med Sci Monit 2012; 18(4): BR156-162
Background: Xeroderma pigmentosum group F (XPF) is an important participant in the nucleotide excision repair process. This study aimed to investigate the expression of DNA repair gene xeroderma pigmentosum group F (XPF) in bladder cancer and its clinical significance.
Material/Methods: Total RNA and protein were extracted from 45 untreated bladder cancer tissues and 21 hydroxycamptothecin (HCPT)-treated bladder cancer specimens. Real-time PCR and Western blot assay were used to detect the mRNA and protein levels of XPF, respectively. siRNA targeting XPF was used to knock down the XPF expression in T24 cells and 5637 cells, and the sensitivity of XPF-depleted cells to HCPT was measured.
Results: The XPF expressions in the HCPT-treated cancer tissues was significantly higher than those in the untreated cancer tissues at both mRNA and protein levels. Importantly, the enhanced XPF expression decreased the sensitivity of T24 cells and 5637 cells to HCPT. Furthermore, the HCPT treatment significantly increased the apoptosis of T24 cells and 5637 cells. Alternatively, after the XPF gene silencing, the chemotherapeutic resistance of bladder cancer cells was significantly decreased.
Conclusions: Our results show the increased expression of XPF is involved in the chemotherapeutic resistance of bladder cancer, and decreasing XPF expression may become a promising therapeutic strategy for bladder cancer.
Keywords: Genes, Neoplasm - genetics, Humans, Gene Silencing - drug effects, Gene Expression Regulation, Neoplastic - drug effects, Drug Screening Assays, Antitumor, Drug Resistance, Neoplasm - genetics, DNA-Binding Proteins - metabolism, DNA Repair - genetics, Cell Line, Tumor, Caspases - metabolism, Camptothecin - therapeutic use, Apoptosis - genetics, RNA, Messenger - metabolism, RNA, Small Interfering - metabolism, Urinary Bladder Neoplasms - pathology