title: X-linked inhibitor of apoptosis-associated factor l (XAFl) enhances the sensitivity of colorectal cancer cells to cisplatin.
abstract: The purpose of present study was to investigate the roles of X-linked inhibitor of apoptosis-associated factor l (XAFl) in regulation apoptosis of colorectal cancer (CRC) cells after treatment with cisplatin (DDP). A total of ten paired cancerous and non-cancerous tissues were collected from patients with CRC after surgery. The levels of XAFl protein were detected by Western blot. Primary CRC cells were separated from cancer tissues, and its viability or apoptosis after treatment with DDP was determined with MTT or Annexin V/PI assays, respectively. Furthermore, we either up-regulated transfecting a XAF1 overexpression vector or down-regulated XAF1 by siRNA interference. And then, the XAF1 levels and its sensitivity to cisplatin were assessed. XAFl had a lower expression in the cancerous tissues from samples T1, T2 and T3 than their paired non-cancerous tissues N1, N2 and N3. However, the expression of XAF1 was not detected in samples T4 and N1. XAF1 levels in cancer tissues significantly decreased in comparison with normal tissues. Cell abilities of primary cells were significantly decreased in a dose-dependent manner, after treatment with a series concentrations of cisplatin (2, 5, 10 μg/mL) for 48 h. Although, after down-expression of XAFl by siRNA, cisplatin caused a significant decreases in apoptosis rates in CRC cells. The up-regulation of XAF1 distinctly increased apoptosis in CRC cells administered by cisplatin (P < 0.001). The XAFl could promoted apoptosis and enhanced chemotherapy sensitivity to cisplatin in CRC cells.
authors.affiliation: Department of Oncology, The Affiliated Luoyang Central Hospital of Zhengzhou University, No. 288 Zhongzhou Road, Luoyang, 471000, China.
authors.forename: Wen-Cui
authors.initials: WC
authors.lastname: Ju
authors.forename: Guo-Bin
authors.initials: GB
authors.lastname: Huang
authors.forename: Xiao-Yong
authors.initials: XY
authors.lastname: Luo
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Ren
authors.forename: De-Qing
authors.initials: DQ
authors.lastname: Zheng
authors.forename: Pin-Jia
authors.initials: PJ
authors.lastname: Chen
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Lou
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C417551:XAF1 protein, human; D002945:Cisplatin