title: Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells.
abstract: X-linked inhibitor of apoptosis (XIAP) is the most potent member of the inhibitor of apoptosis protein (IAP) gene family in terms of its ability to inhibit caspases and suppress apoptosis. Recent evidence has suggested that XIAP is a key determinant in chemoresistance of cancer cells. To explore a novel approach for ameliorating chemotherapy of gastric cancer, the antisense expression vector for the XIAP gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53) and MKN-28 (mutant-type p53). This transfer resulted in significant downregulation of XIAP expression, decreased in vitro cell viabilities, and induced apoptosis. In transferred cells, inactive caspase-3 precursors were cleaved into the active subunits (p20 and p17) during apoptosis induced by downregulation of XIAP. The inhibitory effects of cisplatin and mitomycin C on the growth of XIAP downregulated cancer cells were significantly enhanced. In addition, this process occurred only in wild-type p53 (MKN-45), but not in mutant-type p53 (MKN-28) gastric cancer cells. The data presented suggest that downregulation of XIAP via antisense RNA can lead to apoptosis of gastric cancer cells in vitro, correlating with cellular p53 status and activation of caspase-3. This finding could lead to a potential strategy for improving the efficiency of therapies for gastric cancer.
authors.affiliation: Department of Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. qs_tong@hotmail.com
authors.forename: Qiang-Song
authors.initials: QS
authors.lastname: Tong
authors.forename: Li-Duan
authors.initials: LD
authors.lastname: Zheng
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Fu-Qing
authors.initials: FQ
authors.lastname: Zeng
authors.forename: Fang-Min
authors.initials: FM
authors.lastname: Chen
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Dong
authors.forename: Gong-Cheng
authors.initials: GC
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D016373:DNA, Antisense / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005822:Genetic Vectors; D006801:Humans; D016685:Mitomycin / Q000627:therapeutic use; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy*; D051636:X-Linked Inhibitor of Apoptosis Protein
chemical_list: D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D016373:DNA, Antisense; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D016685:Mitomycin; C505407:CASP3 protein, human; D053148:Caspase 3; D002945:Cisplatin