WRH-2412 alleviates the progression of hepatocellular carcinoma through regulation of TGF-beta/beta-catenin/alpha-SMA pathway

Hepatocellular carcinoma is considered one of the most lethal cancers, which is characterised by increasing prevalence associated with high level of invasion and metastasis. The novel synthetic pyrazolo[3,4-b]pyridine compound, WRH-2412, was reported to exhibit in vitro antitumor activity. This study was conducted to evaluate the antitumor activity of WRH-2412 in HCC induced in rats through affecting the TGF-beta/beta-catenin/alpha-SMA pathway. Antitumor activity of WRH-2412 was evaluated by calculating the rat's survival rate and by assessment of serum alpha-fetoprotein. Protein expression of TGF-beta, beta-catenin, E-cadherin, fascin and gene expression of SMAD4 and alpha-SMA were determined in hepatic tissue of rats. WRH-2412 produced antitumor activity by significantly increasing the rats' survival rate and decreasing serum alpha-fetoprotein. WRH-2412 significantly reduced an HCC-induced increase in hepatic TGF-beta, beta-catenin, SMAD4, fascin and alpha-SMA expression. In addition, WRH-2412 significantly increased hepatic E-cadherin expression. [Graphics]