title: Silencing of X-linked inhibitor of apoptosis decreases resistance to cisplatin and paclitaxel but not gemcitabine in non-small cell lung cancer.
abstract: Non-small cell lung cancer (NSCLC) is a highly lethal malignancy that often becomes resistant to chemotherapy. The effect of silencing the X-linked inhibitor of apoptosis gene (XIAP) on resistance to cisplatin, paclitaxel and gemcitabine was studied in the NSCLC cell lines A549  and H460. Transfection of these cells with small interfering RNA (siRNA) for XIAP blocked overexpression of the gene, suppressed cell proliferation, increased apoptosis and increased the cells' sensitivity to cisplatin and paclitaxel by preventing the binding of XIAP to caspase3 and  increasing the activity of this enzyme. There was no significant difference in resistance to gemcitabine between XIAP-silenced cells and non-transfected cells. Changes in chemoresistance were independent of the activity of caspase-9. Silencing XIAP with siRNA can decrease chemoresistance  in NSCLC and may have a potential role in the treatment of this disease.
authors: Department of Immunology, Harbin Medical University, Harbin, Heilongjiang, China.
authors: Y
authors: Y
authors: Liu
authors: X
authors: X
authors: Wu
authors: Y
authors: Y
authors: Sun
authors: F
authors: F
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D034622:RNA Interference; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics* / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D051636:X-Linked Inhibitor of Apoptosis Protein; D003841:Deoxycytidine; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine