Mechanism of Killing Effect of Thioridazine on Human Lung Cancer PC9 Cells
10.3779/j.issn.1009-3419.2015.12.03
- VernacularTitle:硫利达嗪对肺癌PC9细胞的杀伤效应及其机制
- Author:
GONG LI
1
;
WANG YI
;
TONG SIHAO
;
LIU LIU
;
NIU LING
;
YUAN YUAN
;
BAO YANGYI
Author Information
1. 安徽医科大学第三附属医院 合肥市第一人民医院 肿瘤科
- Keywords:
Lung cancer;
hTioridazine;
Apoptosis;
Caspase apoptotic pathway
- From:
Chinese Journal of Lung Cancer
2015;(12):727-733
- CountryChina
- Language:Chinese
-
Abstract:
Background and objectiveRecent research shows thioridazine which is a kind of phenothiazine anti-psychotic drugs can inhibit the proliferation of various tumor cellsin 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.MethodsAtfer 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 hTe proliferation of PC9 cells was signiifcantly 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 signiifcantly increased with the increasing concentration of thioridazine. Compared with the control group, the differences were statistically signiifcant (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).ConclusionhTe 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.
