Synergistic effect of scopadulciol in treating human prostate cancer by TK-dependent ganciclovir

Abstract

Objective To investigate the synergistic efect of scopadulciol (SDC) on the killing effect on antitumor actions by Ad-hTERT-HSV-tk/ganciclovir (GCV) suicide gene system on prostate cancer cells in vitro.Methods To clarify the mechanism of enhanced effect of SDC in the gene therapy of human prostate cancer by TK-dependent GCV in molecular level,the TK enzyme activity and the concentration of GCV-TP in the tumor cells were measured by using high performance liquid chromatography (HPLC).The prostate cancer cells,respectively,were treated with Ad-hTERT-HSV-tk or GCV in combination with SDC with different doses and different concentrations.The killing effect and the bystander effect of these drugs in the therapy of human prostate cancer cells were observed.Results SDC had slightly effect on the TK enzyme activity of LNCaP and PC3 cells that were transduced by Ad-hTERT-HSV-tk.The GCV-TP concentration in the GCV treatment group was 100％.The GCV-TP concentration was ( 101.0 ± 1.5) ％ when 0.04 μmol/L SDC was added,but there was no significant difference.The GCV-TP concentration was up to ( 106.0 ± 4.5) ％ when adding 0.20 μmol/L SDC that was 5-fold higher for the dose of the therapy,and there was significant difference campared to the GCV treatment group (P＜0.05).It was confirmed that SDC had strong bystander effect and weak killing effect on the prostate cancer cells by conbination of Ad-hTERT-HSV-tk and GCV.Conclusion The synergistic effect of SDC is significantly shown in the therapy of human prostate cancer cells by TK-dependent GCV.SDC is effective in the Ad-hTERT-HSV-tk/GCV administration system in killing prostate cancer cells. Key words: Prostate cancer; Gene therapy; Recombinant adenovirus; Telomerase reverse transcriptase