Dially trisulfide enhancing killing effects of herpes simplex virus thymidine kinase / ganciclovir system against prostate cancer cells

Abstract

Objective To investigate the killing effect of herpes simplex virus thymidine kinase /ganciclovir (HSV-TK/GCV) system combined with diallyl trisulfide (DATS) on prostate cancer cell line PC-3 and the mechanism.Methods TK gene was transfected into PC-3 cells with lipofectamine. Cell viability was determined using methyl thiazol tetrazolium (MTT) assay. Apoptosis was assessed by flow cytometry. Protein levels of apoptosis regulating proteins were detected by using Western blotting. The activity of Caspase-3 was measured using a colorimetric assay.Results GCV or DATS alone could inhibit the proliferation of PC-3/TK cells. In GCV + DATS group,the cell viability was decreased to ( 35.0 ± 2.8) ％as compared with that in 5 μmol/L GCV group [ (68.0 ± 1.8) ％ ] and 15 μmol/L DATS group [ (63.9 ±5.9) ％ ], suggesting the synergic effects of GCV and DATS. Apoptosis rate in GCV + DATS group was higher than in GCV alone group and DATS alone group. The combined use of GCV + DATS could significantly reduce the expression of B lymphocytes/leukemia-2 (bcl-2) and bcl-xL,promote the release of cytochrome c and the cleavage of Caspase-9,and enhance the activity of Caspase-3.Conclusion The combination of HSV-TK/GCV system with DATS can inhibit the proliferation of prostate cancer cells synergically through inducing apoptosis,which may be correlated with the down-regulation of bcl-2 and bcl-xL,the release of cvtochrome c, the cleavage of Caspase-9 and the activation of Caspase-3. Key words: Prostate cancer; Diallyl trisulfide; Gene therapy