title: [Inhibition of mitochondrial Smac release by Akt in chemoresistant ovarian cancer cells].
abstract: OBJECTIVE
  To investigate the relationship between Akt and second mitochondria-derived activator of caspases (Smac) in cisplatin (CDDP)-induced apoptosis in human ovarian cancer cells and the role of Akt in the molecular mechanism of chemoresistance in ovarian cancer.
  
  
  METHODS
  Chemosensitive (OV2008 and A2780s) and chemoresistant (C13* and A2780cp) ovarian cancer cell lines were treated with CDDP and subcellular Smac contents were determined by Western blot. Smac siRNA and Smac N7 peptide were transfected into OV2008 and C13* cells, respectively. CDDP-induced apoptosis was measured by flow cytometry. A2780s cells stably transfected with Akt2 (A2780s-AAkt2) and C13* cells transfected with Aktl/2 siRNA were treated with CDDP, and Smac content and apoptosis in the cells were determined to detect the changes of their chemoresistance to CDDP.
  
  
  RESULTS
  CDDP induced mitochondrial Smac release and apoptosis in chemosensitive cells (P < 0.05), but not resistant cells (P > 0.05). Downregulation of Smac by Smac siRNA confer resistance in OV2008 cells and Smac N7 peptide sensitized C13* cells to CDDP treatment. Overexpression of Akt2 inhibited mitochondrial Smac release and downregulation of Akt by siRNA sensitized C13* cells to CDDP treatment.
  
  
  CONCLUSIONS
  Smac is required in CDDP-induced apoptosis in ovarian cancer cells and overexpression of Akt inhibits mitochondrial Smac release. Akt is closely related to the chemoresistance of ovarian cancer.
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, China.
authors.forename: Xiao-Kui
authors.initials: XK
authors.lastname: Yang
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Wang
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Wang
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin