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. 1999 May;80(5-6):705–710. doi: 10.1038/sj.bjc.6690413

Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α

W-C Hung 1, L-Y Chuang 2
PMCID: PMC2362280  PMID: 10360647

Abstract

Although interferon-α (IFN-α) has shown great promise in the treatment of chronic viral hepatitis, the anti-tumour effect of this agent in the therapy of liver cancer is unclear. Recent studies have demonstrated that differentiation-inducing agents could modulate the responsiveness of cancer cells to IFN-α by regulating the expression of signal transducers and activators of transcription (STAT) proteins, a group of transcription factors which play important roles in the IFN signalling pathway. We have reported that sodium butyrate is a potent differentiation inducer for human hepatoma cells. In this study, we investigated whether this drug could regulate the expression of STAT proteins and enhance the anti-tumour effect of IFN-α in hepatoma cells. We found that sodium butyrate specifically activated STAT1 gene expression and enhanced IFN-α-induced phosphorylation and activation of STAT1 proteins. Co-treatment with these two drugs led to G1 growth arrest, accompanied by down-regulation of cyclin D1 and up-regulation of p21WAF-1, and accumulation of hypophosphorylated retinoblastoma protein in hepatoma cells. Additionally, internucleosomal DNA fragmentation, a biological hallmark of apoptosis, was detected in hepatoma cells after continuous incubation with a combination of these two drugs for 72 h. Our results show that sodium butyrate potently enhances the anti-tumour effect of IFN-α in vitro and suggest that a rational combination of these two drugs may be useful for the treatment of liver cancer. © 1999 Cancer Research Campaign

Keywords: sodium butyrate, interferon, hepatoma, cyclin D1, p21WAF-1, retinoblastoma protein, apoptosis

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Selected References

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