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

AbstractHepatocellular 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. T...

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Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/14756366.2023.2185761
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Summary:AbstractHepatocellular 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.
ISSN:1475-6366
1475-6374