title: Knockdown of PLA2G2A sensitizes gastric cancer cells to 5-FU in vitro.
abstract: OBJECTIVE
  Elevated expression of the PLA2G2A phospholipase in gastric cancer (GC) is associated with improved patient survival. PLA2G2A is also an important regulator of proliferation, invasion and metastasis in GC. However, no relation about PLA2G2A and chemosensitivity in GC cells was reported. 5-Fluorouracil (5-FU) is widely used for treatment of advanced gastric cancer. However, it is common for such patients to develop resistance to 5-FU, and this drug resistance becomes a critical problem for chemotherapy. The mechanisms underlying this resistance are largely unknown. In the present study, we investigated whether PLA2G2A could confer 5-FU resistance or sensitise in GC cells in vitro.
  
  
  METHODS
  The 5-FU sensitivity of GC cell lines SGC-7901, MKN-45, RF-48, N87, AGS, MKN-28, RF-1, MGC-803 were determined by MTT assays. PLA2G2A levels were determined by western blot assays. The effects of 5-FU on PLA2G2A expression were determined in vitro. PLA2G2A was inhibited by silencing of the PLA2G2A using small interfering RNA in vitro. PLA2G2A was overexpressed by transfection of full-long PLA2G2A cDNA in vitro, and the effects were evaluated on 5-FU sensitivity.
  
  
  RESULTS
  The cell lines SGC-7901, MKN-45, RF-48 and N87 were sensitive, whereas AGS, MKN-28, RF-1 and MGC-803 were resistant to 5-FU. Significant correlation was observed between basal PLA2G2A and 5-FU sensitivity. Silencing of PLA2G2A increased 5-FU killing in 5-FU-treated cells, and overexpression of PLA2G2A decreased 5-FU killing in 5-FU-treated cells.
  
  
  CONCLUSIONS
  PLA2G2A was correlated with sensitivity to 5-FU. Silencing of PLA2G2A was sensitive to 5-FU treatment. Thus, PLA2G2A may be a useful therapeutic target for a subset of gastric cancers.
authors.affiliation: Department of General Surgery, Qingdao University, Qingdao, Shandong, Reople's Republic of China. chendd820@126.com
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: X-L
authors.initials: XL
authors.lastname: Jiao
authors.forename: Z-K
authors.initials: ZK
authors.lastname: Liu
authors.forename: M-S
authors.initials: MS
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Niu
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005472:Fluorouracil / Q000627:therapeutic use*; D005822:Genetic Vectors; D054501:Group II Phospholipases A2 / Q000235:genetics*; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection
chemical_list: D000963:Antimetabolites; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human; C022616:thiazolyl blue; D005472:Fluorouracil