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

WRH-2412通过调节TGF-β/β-catenin/α-SMA通路减缓肝细胞癌进展

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作者:Mohammed A F Elewa, Wagdy M Eldehna, Ahmed M E Hamdan, Samraa H Abd El-Kawi, Asmaa M El-Kalaawy, Taghreed A Majrashi, Reham F Barghash, Hatem A Abdel-Aziz, Khalid S Hashem, Mohammed M H Al-Gayyar

Abstract

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-β/β-catenin/α-SMA pathway. Antitumor activity of WRH-2412 was evaluated by calculating the rat's survival rate and by assessment of serum α-fetoprotein. Protein expression of TGF-β, β-catenin, E-cadherin, fascin and gene expression of SMAD4 and α-SMA were determined in hepatic tissue of rats. WRH-2412 produced antitumor activity by significantly increasing the rats' survival rate and decreasing serum α-fetoprotein. WRH-2412 significantly reduced an HCC-induced increase in hepatic TGF-β, β-catenin, SMAD4, fascin and α-SMA expression. In addition, WRH-2412 significantly increased hepatic E-cadherin expression.

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