title: Transfection of Smac/DIABLO sensitizes drug-resistant tumor cells to TRAIL or paclitaxel-induced apoptosis in vitro.
abstract: Smac/DIABLO is a recently identified protein released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing inhibitor of apoptosis proteins (IAPs). In this study, we observed depressed Smac/DIABLO and increased XIAP expression in ovarian epithelial tissues ordered by normal, benign and malignant epithelia. In epithelial ovarian cancer (EOC), the expression of Smac/DIABLO decreased with the malignancy. Smac/DIABLO expression showed no correlation with TRAIL sensitivity, while lower Smac/DIABLO expression and decreased release of Smac/DIABLO from mitochondria upon apoptosis stimuli were observed in paclitaxel-resistant A2780/pac cells as compared to the sensitive controls. Ectopic Smac/DIABLO alone inhibited cell growth, arrested cells in G0/G1 phase, and sensitized drug-resistant EOC cells to TRAIL or paclitaxel-induced apoptosis. Increased apoptosis was associated with the down-regulation of XIAP, FLIP, and up-regulation of Smac/DIABLO, cytochrome c, p53, along with increased activity of caspase-3. Thus, over-expression of Smac/DIABLO is a promising strategy for drug-resistant ovarian cancer treatment.
authors.affiliation: Department of Obstetrics and Gynecology, QiLu Hospital of ShanDong University, Jinan, ShanDong 250012, China.
authors.forename: Hong Luan
authors.initials: HL
authors.lastname: Mao
authors.forename: Pei Shu
authors.initials: PS
authors.lastname: Liu
authors.forename: Jing Fang
authors.initials: JF
authors.lastname: Zheng
authors.forename: Pei Hai
authors.initials: PH
authors.lastname: Zhang
authors.forename: Li Guang
authors.initials: LG
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Xin
authors.forename: Chunxi
authors.initials: C
authors.lastname: Liu
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D014162:Transfection; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D017239:Paclitaxel