title: [Study on the mechanism of DDP-resistance mediated by phosphate JNK in gastric cancer].
abstract: OBJECTIVE
  To investigate the mechanism of DDP-resistance in gastric cancer cell line SGC7901/DDP mediated by phosphate(p)-JNK.
  
  
  METHODS
  The p-JNK expression was blocked by the JNK inhibitor SP600125. The drug sensitivity was detected by MTT. Cell apoptosis rate was measured by flow cytometry. The expression of p-JNK and P-glycoprotein (P-gp) was examined by Western blot. The expression of both proteins were detected in a tissue microarray containing 168 spots of cancer tissue and 27 spots of normal gastric tissue by SP immunohistochemistry. Pearson method was used to analyze the correlation between p-JNK and P-gp.
  
  
  RESULTS
  The drug sensitivity and cell apoptosis rate significantly increased (P<0.01), and the protein expression levels of p-JNK and P-glycoprotein were down-regulated after the inhibition of p-JNK by SP600125 in both SGC7901(p-JNK: 1.17+/-0.03 vs 0.38+/-0.071, P-gp: 0.21+/-0.01 vs 0.06+/-0.01) and SGC7901/DDP (p-JNK: 2.56+/-0.14 vs 1.02+/-0.12, P-gp: 0.77+/-0.05 vs 0.52+/-0.06 )cells(all P<0.01). The protein expression rates of p-JNK and P-glycoprotein were 45.8% and 51.8% respectively in gastric cancer tissue, which were significantly higher than those in normal gastric tissue 7.4% and 18.5% (P<0.01). The correlation of protein expression of p-JNK and P-gp was positive (P<0.01).
  
  
  CONCLUSIONS
  JNK anti-apoptosis pathway with the regulation of P-gp expression plays an important role in the DDP-resistance of gastric cancer, which may be a novel target for reversing multidrug resistance.
authors.affiliation: Department of General Surgery, The First People's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Peng
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Li
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Mian-Zhi
authors.initials: MZ
authors.lastname: Zhao
authors.forename: Qing
authors.initials: Q
authors.lastname: Wu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D048031:JNK Mitogen-Activated Protein Kinases; D002945:Cisplatin