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

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.

GRAPHICAL ABSTRACT

Keywords:

• Alpha smooth muscle actin (α-SMA)
• E-cadherin
• hepatocellular carcinoma
• pyrazolo[34-b]pyridine
• SMAD4
• transforming growth factor (TGF)-β

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Correction

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/10.1080/14756366.2023.2218746)

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through Small Groups Project under [grant number (RGP.1/346/43)].