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WRH-2412 通过调控 TGF-β/β-catenin/α-SMA 通路缓解肝细胞癌的进展。

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

机构信息

Biochemistry Department, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh, Egypt.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt.

出版信息

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2185761. doi: 10.1080/14756366.2023.2185761.

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-]pyridine compound, , was reported to exhibit antitumor activity. This study was conducted to evaluate the antitumor activity of in HCC induced in rats through affecting the TGF-β/β-catenin/α-SMA pathway. Antitumor activity of 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. produced antitumor activity by significantly increasing the rats' survival rate and decreasing serum α-fetoprotein. significantly reduced an HCC-induced increase in hepatic TGF-β, β-catenin, SMAD4, fascin and α-SMA expression. In addition, significantly increased hepatic E-cadherin expression.

摘要

肝细胞癌被认为是最致命的癌症之一,其特征是发病率不断增加,侵袭和转移程度高。新型合成吡唑并[3,4-d]嘧啶化合物 ,被报道具有抗肿瘤活性。本研究旨在通过影响 TGF-β/β-catenin/α-SMA 通路,评估 在诱导大鼠肝癌中的抗肿瘤活性。通过计算大鼠的存活率和评估血清甲胎蛋白来评估 的抗肿瘤活性。测定大鼠肝组织中 TGF-β、β-catenin、E-cadherin、 fascin 和 SMAD4、α-SMA 的基因表达。 显著提高了大鼠的存活率,降低了血清甲胎蛋白,从而发挥抗肿瘤作用。 显著降低了 HCC 诱导的肝 TGF-β、β-catenin、SMAD4、 fascin 和 α-SMA 表达的增加。此外, 显著增加了肝 E-cadherin 的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/704d/10013371/a5b273838ed0/IENZ_A_2185761_UF0001_C.jpg

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