Sodium Butyrate Induces Growth Inhibition and Apoptosis in Human Prostate Cancer DU145 Cells by Up-Regulation of the Expression of Annexin A1Reportar como inadecuado




Sodium Butyrate Induces Growth Inhibition and Apoptosis in Human Prostate Cancer DU145 Cells by Up-Regulation of the Expression of Annexin A1 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

Sodium butyrate, a histone deacetylase inhibitor, has emerged as a promising anticancer drug for multiple cancers. Recent studies have indicated that sodium butyrate could inhibit the progression of prostate cancer; however, the exact mechanism is still unclear. The aim of this study was to investigate the mechanism of sodium butyrate action in prostate cancer DU145 cells.

Methods

The inhibitory effects of NaB on cell growth were detected by the 3-4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrrazolium bromide assay. Cell apoptosis was determined by flow cytometric analysis of DU145 cells stained with annexin V and PI. Hoechst 33258 and fluorescence microscopes were used to observe the nuclear morphology of DU145 cells after treatment with NaB. ANXA1 knockdown cells were established through transfection with ANXA1 siRNA. ANXA1 mRNA levels were measured by qRT-PCR. Bcl-2, Bax, ANXA1, ERK1-2 and pERK1-2 were detected by western blot.

Results

NaB significantly inhibited the growth and induction apoptosis of DU145 and PC3 cells in a dose-dependent manner. Expression of the anti-apoptosis gene Bcl-xl and Bcl-2 in DU145 cells are decreased and expression of the pro-apoptosis gene Bax and Bak increased after NaB treatment. Further studies have demonstrated that NaB up-regulated the expression of ANXA1 and that the tumor inhibition action of NaB was reduced markedly through knockdown of the ANXA1 gene in DU145 cells. Moreover, the siANXA1 cells showed that cell proliferation increased and cell apoptosis was induced by the inactivation of extracellular regulated kinase ERK.

Conclusion

Our results support a significant correlation between NaB functions and ANXA1 expression in prostate cancer, and pave the way for further studying the molecular mechanism of NaB actions in cancers.



Autor: Dawei Mu, Zhuo Gao, Heqing Guo , Gaobiao Zhou, Bin Sun

Fuente: http://plos.srce.hr/



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