title: Identification of triosephosphate isomerase as an anti-drug resistance agent in human gastric cancer cells using functional proteomic analysis.
abstract: OBJECTIVE
  Proteomic study was used to explore new multidrug resistance (MDR)-related proteins and clarify novel mechanism of MDR in gastric cancer.
  
  
  METHODS
  Two-dimensional gel electrophoresis and the PDQuest software analysis were applied to compare the differential expression of MDR-related proteins in gastric cancer SGC7901 cells and drug-resistant SGC7901 cells (SGC7901/VCR) induced by vincristine sulfate (VCR). The differential protein dots were excised and further analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis (MALDI-TOF-MS).
  
  
  RESULTS
  Nine differential expression proteins between the two cell lines were successfully identified by MALDI-TOF-MS. Triosephosphate isomerase (TPI), a glycolytic pathway enzyme, was identified as a downregulated protein in SGC7901/VCR cells. Further, Western blot analysis and semiquantitative RT-PCR confirmed its decreased expression in SGC7901/VCR cells. Sense vector pcDNA3.1-TPI was constructed and transfected into SGC7901/VCR. The sensitivity of TPI-SGC7901/VCR cells to adriamycin (ADR), VCR, 5-fluorouracil and cis-dichlorodiamine platinum, as well as the accumulation and retention to ADR, were significantly increased when compared to their control cell lines.
  
  
  CONCLUSIONS
  These results provide new MDR-related protein candidates, which are differentially expressed in the MDR cell line and its parental cell line including TPI, which may participate in the VCR-mediated MDR in human gastric cancer. Upregulation of TPI expression could partially reverse multidrug-resistant phenotype of SGC7901/VCR, which suggests that TPI may be an anti-drug resistance agent in gastric cancer and the candidate target to develop novel therapeutics for better treatment of gastric cancer.
authors.affiliation: State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yang
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.forename: Mei
authors.initials: M
authors.lastname: Lan
authors.forename: Zhenxiong
authors.initials: Z
authors.lastname: Liu
authors.forename: Huihong
authors.initials: H
authors.lastname: Zhai
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D006801:Humans; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014305:Triose-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D014305:Triose-Phosphate Isomerase