Abstract:

Objective To investigate the growth inhibitory effects of β-hydroxyisovalerylshikonin (β-HIVS) on hormone-independent prostate cancer cell line PC-3, and explore the related mechanism. Methods The inhibition rates of β-HIVS on PC-3 cells and normal human skin fibroblasts (HSF) were determined by MTT method. Luciferase reporter assay was adopted to examine the transcriptional activity of hypoxia-inducible factor-1 (HIF-1) and nuclear factor-kappa B (NF-κB). The expression of vascular endothelial growth factor (VEGF), the target gene of HIF-1, was detected by RT-PCR. The expression of HIF-1α protein in PC-3 cells treated by β-HIVS was detected by Western blotting. Results β-HIVS significantly inhibited the growth of PC-3 cells (P<0.05), while had no significant effect on HSF cells (P>0.05). There was no significant change in transcriptional activity of NF-κB in PC-3 cells after drug treatment (P>0.05). β-HIVS inhibited the transcriptional activity of HIF-1 and decreased the expression of VEGF. The protein level of HIF-1α in PC-3 cells was reduced by β-HIVS. Conclusion β-HIVS inhibits the growth of PC-3 cells by decreasing the level of HIF-1α protein in PC-3 cells under hypoxia condition, thus attenuating the transcriptional activity of HIF-1α and decreasing the expression of VEGF.

Key words: β-hydroxyisovalerylshikonin, prostate cancer, hypoxia-inducible factor-1, vascular endothelial growth factor