title: [Effect of co-inhibition of MCT1 gene and NHE1 gene on proliferation and growth of human lung adenocarcinoma cells].
abstract: OBJECTIVE
  The authors previously discovered that the intracellular pH values (pHi) of tumor cells could be decreased, which led tumor cells to acidify and die, when the expressions of the first subtype of monocarboxylate transporter (MCT1) gene and the first subtype of Na+/H+ exchanger (NHE1) gene in tumor cell membranes had been inhibited by each corresponding antisense gene respectively. However it was not clear whether there were co-effects on the pHi, proliferation, and growth of tumor cells, after two genes were inhibited at the same time.
  
  
  METHODS
  pLXSN-MCT1 and pLXSN-NHE1, the corresponding antisense gene expression vectors of MCT1 and NHE1 genes, were introduced into human lung adenocarcinoma A549 cells at the same time with electroporation. The positive colonies were selected by G418. Using PCR and RT-PCR technique, it was confirmed that antisense genes of MCT1 and NHE1 genes integrated with A549 genomic DNA. The pHi and lactate content were detected with spectrophotometry. Cell growth cycle was measured with flow cytometer. The cells co-transfected antisense genes, cells transfected MCT1 antisense gene and A549 cells were respectively inoculated in nude mouse subcutaneous to observe the growth of transplantation tumors.
  
  
  RESULTS
  Compared with A549 cells, the pHi of cells co-transfected antisense genes was remarkably decreased (P < 0.05), while lactate content was remarkably increased (P < 0.001). The cell cycle was blocked at G0-G1 period. And the transplantation tumors of nude mice inoculated co-transfected antisense gene-cells and inoculated MCT1-antisense-gene-transfected cells were significantly lighter and smaller than ones inoculated A549 cells (P < 0.001).
  
  
  CONCLUSIONS
  MCT1 and NHE1 genes play important regulation roles in proliferation and growth of tumor cells, probably by affecting pHi.
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P. R. China. zhanggz7781@sina.com
authors.forename: Gui-zhi
authors.initials: GZ
authors.lastname: Zhang
authors.forename: Gui-jun
authors.initials: GJ
authors.lastname: Huang
authors.forename: Wei-liang
authors.initials: WL
authors.lastname: Li
authors.forename: Guo-ming
authors.initials: GM
authors.lastname: Wu
authors.forename: Gui-sheng
authors.initials: GS
authors.lastname: Qian
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016373:DNA, Antisense / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D009368:Neoplasm Transplantation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D027981:Symporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D016373:DNA, Antisense; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D017923:Sodium-Hydrogen Exchangers; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1