title: [The role of the K+ channel in the inhibition of the human lung adenocarcinoma cell proliferation by rmhTNF].
abstract: BACKGROUND
  With the development of patch clamp and molecular biology technique, and the application of them in the investigation of tumor cellular membrane ion channnel, the ion channel is becoming the hot spot of the tumor base research gradually. The aim of this study is to investigate the electrophysiological properties of human lung adenocarcinoma cell line A-549 and the role of K+ channel in inhibition of cell proliferation by the recombinant mutant human tumor necrosis factor (rmhTNF).
  
  
  METHODS
  Ionic currents were recorded using the whole-cell patch clamp recording technique. The proliferation activity of A-549 cells was measured by MTT assay. The cell cycle and apoptosis rates of the carcinoma cells were measured by flow cytometric analysis (FCM).
  
  
  RESULTS
  Whole-cell patch clamp recording revealed a voltage-gated K+ current in A-549 cells, which could be blocked by the K+ channel blocker, TEA and CsCl. The amplitude of K+ current was markedly diminished in all cells incubated with different concentration of rmhTNF (P < 0.01). Obvious inhibitive effect of rmhTNF on proliferation of the cells was found in vitro in a dose-dependent manner (P < 0.01), the maximal inhibitory rate was 38.68% when the concentration was 400U/mL. The rmhTNF inhibited the cell cycle shifting from G1 phase to S phase and promoted apoptosis as determined by FCM analysis. The proportion of G1 cells increased from 53.02% to 72.93%, and the apoptosis rate increased from 2.08% to 8.68%. The difference were significant between the control and the high concentration groups ( 200U/mL and 400U/mL) (P < 0.01).
  
  
  CONCLUSIONS
  rmhTNF exerts its cytotoxic effects on A-549 cells through inhibiting cell cycle shifting and inducing apoptosis. The K+ channels on the A-549 cell membrane can be blocked by rmhTNF partly, and the effect of inhibiting proliferation and activating apoptosis on A-549 cells is a result of depression of the K+ channel.
authors.affiliation: Department of Thoracocardiac Surgery, Luzhou Medical College Hospital, Luzhou, Sichuan 646000, P.R.China.
authors.forename: Zonglin
authors.initials: Z
authors.lastname: Wang
authors.forename: Tianyang
authors.initials: T
authors.lastname: Dai
authors.forename: Fusheng
authors.initials: F
authors.lastname: Zhan
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zeng
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang