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.

Stimulation of the hypoxia pathway modulates chemotherapy resistance in Hodgkin’s lymphoma cells

“…In hepatocellular carcinomas, the increased expression of XAF1 leads to an inhibition of tumor angiogenesis [64,67,68]. In ovarian carcinoma and colorectal cancer cells, the overexpression of XAF1 leads to a sensitization of the cells for cisplatin [69,70]. This fits to the observation that a reduced XAF1 expression leads to increased cisplatin resistance.…”

Lentivirus-mediated downregulation of MAT2B inhibits cell proliferation and induces apoptosis in melanoma

“…XIAP-associated factor 1 (XAF1) was identified as a XIAP-binding protein and could directly bind preferentially to XIAP and antagonize the anti-caspase activity of XIAP to induce apoptosis (26). Pro-apoptotic gene XAF1 was constantly expressed in normal and fetal tissues but weakly expressed in most human cancer cell lines and human cancer tissues such as ovarian, hepatocellular, colon, pancreatic cancer and melanoma (27)(28)(29)(30)(31). Recent studies had shown that XAF1 expression was relatively low in hepatocellular carcinoma cell lines and hepatoma tissues.…”

Aberrant splicing and drug resistance in AML

“…For example, a pro-apoptotic Smac3 splice variant of Smac/Diablo was found to accelerate XIAP autoubiquitination and destruction and enhanced apoptotic cell death in HeLa cells exposed to multiple chemotherapeutics [ 80 ]. XAF1 is a pro-apoptotic protein that also targets XIAP and can enhance tumor cell susceptibility to cisplatin [ 81 ] and radiotherapy [ 82 ]. While XAF1 expression in tumor cells is generally very low, quantities of alternatively spliced truncated isoforms lacking the XIAP interaction have been found to increase in some aggressive cancers and have been suggested as potential biomarkers of disease status [ 83 , 84 ].…”