Objective      To determine the effect of thioridazine

a dopamine D2 receptor (DRD2) inhibitor

on the proliferation and apoptosis of ovarian cancer cell lines and investigate the potential mechanism.       Methods      After being treated with thioridazine (0

5

10

15 and 20 μmol/L)

the proliferation of ovarian cancer cell lines SKOV3 and A2780 was respectively measured by CCK-8 assay

and cell apoptosis was determined by DAPI nuclear staining and flow cytometry. DCFH-DA staining was employed to observe the level of reactive oxygen species (ROS). Comet assay was applied to detected nuclear DNA damage. JC-1 staining was used to detect mitochondrial membrane potential. The expression of P53

Bax

Bcl

cytochrome C and active Casepase-3 was assessed by Western blotting.       Results      The proliferation of SKOV3 and A2780 was suppressed by thioridazine in a dose-dependent manner (P0.05). Flow cytometry indicated that the apoptotic rate was significantly higher in the cells after thioridazine treatment (P0.05)

and DAPI staining showed typical apoptotic features

including karyopyknosis

fragmentation

and apoptotic bodies. DCFH-DA staining showed the level of ROS was increased compared to control group (P0.05). Comet assay suggested increased DNA damage

and JC-1 staining indicated decreased mitochondrial membrane potential compared to control group. Western blot analysis found that the expression of P53

Bax

Cytoplasm cytochrome C

active Caspase-3 was increased

while that of Bcl

mitochondrial cytochrome C was decreased.       Conclusion      Thioridazine may induces apoptosis via DNA damage and activation of mitochondrial pathway in ovarian cancer SKOV3 and A2780 cells.