title: Programmed cell death 4 (PDCD4) enhances the sensitivity of gastric cancer cells to TRAIL-induced apoptosis by inhibiting the PI3K/Akt signaling pathway.
abstract: OBJECTIVE
  Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is thought to be a promising anti-neoplastic agent because of its ability to selectively induce apoptosis in cancer cells. However, some cancer cells are resistant to TRAIL. The mechanisms underlying this resistance are unclear. The aim of this study was to explore the role of programmed cell death 4 (PDCD4) in regulating TRAIL sensitivity in gastric cancer cells.
  
  
  METHODS
  PDCD4 complementary DNA and PDCD4-specific short-hairpin RNA (shRNA) fragments were transfected into TRAIL-sensitive and -resistant gastric cancer cells. Expression of PDCD4 and Akt was detected via western blot. Cell survival and apoptosis were measured using 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM) assays.
  
  
  RESULTS
  We found that upregulation of PDCD4 enhanced TRAIL sensitivity in gastric cancer cells. Downregulation of PDCD4 decreased TRAIL sensitivity. Inhibition of Akt by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 induced PDCD4 activity and enhanced TRAIL sensitivity in TRAIL-resistant gastric cancer cells.
  
  
  CONCLUSIONS
  We demonstrated that PDCD4 regulates TRAIL sensitivity in gastric cancer cells by inhibiting the PI3K/Akt signaling pathway.
authors.affiliation: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Wang
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Sun
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Peng
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Yang
authors.forename: Rong-Quan
authors.initials: RQ
authors.lastname: Wang
authors.forename: Dian-Chun
authors.initials: DC
authors.lastname: Fang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D055785:Gene Knockdown Techniques; D006801:Humans; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; C114487:PDCD4 protein, human; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt