title: [Mechanism of Killing Effect of Thioridazine on Human Lung Cancer PC9 Cells].
abstract: BACKGROUND
  Recent research shows thioridazine which is a kind of phenothiazine antipsychotic drugs can inhibit the proliferation of various tumor cells in vitro, but the role of thioridazine on lung cancer has not been reported. So we choose PC9 cell lines as the research object, the aim is to oberve the killing effect of thioridazine on PC9 cells and investigate its possible mechanism.
  
  
  METHODS
  After being treated with different concentrations of thioridazine, the proliferation of PC9 cells was determined by methyl thiazolyltetrazolium (MTT) assay. Flow cytometry was used to measure the cell cycle distribution and apoptosis. The expressions of cell cycle-associated protein CyclinD1 and apoptosis-related proteins Caspase-3, Caspase-8, Caspase-9, Bcl-2, Bax and Bcl-xl were detected by Western blot.
  
  
  RESULTS
  The proliferation of PC9 cells was significantly inhibited by thioridazine in a dose- and time-dependent manner. Flow cytometry showed that cell cycle was arrested in G0/G1 phase and the apoptotic rates were significantly increased with the increasing concentration of thioridazine. Compared with the control group, the differences were statistically significant (P<0.05). Western blot analysis showed that, compared with the control group, thioridazine reduced the expressions of CyclinD1, Bcl-2 and Bcl-xl (P<0.01) and increased the expression of Bax (P<0.01). In the mean time, thioridazine promoted the activities of Caspase-3, Caspase-8 and Caspase-9 (P<0.01).
  
  
  CONCLUSIONS
  The mechanism of thioridazine inhibiting the proliferation of PC9 cells may be related to stimulation of Caspase apoptotic pathway, down-regulation of CyclinD1, Bcl-2, Bcl-xl and up-regulation of Bax.
authors.affiliation: Department of Oncology, the Third Affiliated Hospital of Anhui Medical University, Hefei 230061, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.affiliation: Department of Oncology, the Third Affiliated Hospital of Anhui Medical University, Hefei 230061, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology, the Third Affiliated Hospital of Anhui Medical University, Hefei 230061, China.
authors.forename: Sihao
authors.initials: S
authors.lastname: Tong
authors.affiliation: Department of Oncology, the Third Affiliated Hospital of Anhui Medical University, Hefei 230061, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Oncology, the Third Affiliated Hospital of Anhui Medical University, Hefei 230061, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Niu
authors.affiliation: Central Laboratory of Hefei Binhu Hospital, Hefei 230061, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Oncology, the Third Affiliated Hospital of Anhui Medical University, Hefei 230061, China.
authors.forename: Yangyi
authors.initials: Y
authors.lastname: Bao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013881:Thioridazine / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053181:Caspase 8; D013881:Thioridazine