School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
Medicina (Kaunas). 2022 Jun 14;58(6):798. doi: 10.3390/medicina58060798.
: PNU-74654, a Wnt/β-catenin inhibitor, has reported antitumor activities; however, the therapeutic potential of PNU-74654 in hepatocellular carcinoma (HCC) has not been investigated in detail. The aim of this study was to clarify the cytotoxic effects of PNU-74654 against HCC and to uncover its molecular mechanism. : HepG2 and Huh7 liver cancer cell lines were selected to determine the antitumor properties of PNU-74654. Survival of the liver cancer cells in response to PNU-74654 was assessed by cell viability assays, and the apoptosis effect of PNU-74654 was analyzed by flow cytometry and visualized by Hoechst staining. An oncology array was used to explore the underlying molecular routes of PNU-74654 action in the cells. The migration properties were examined with a wound healing assay, and western blotting was conducted to evaluate protein expression. : Treatment with PNU-74654 decreased cell viability and inhibited cell migration. The cell cycle analysis and Hoechst staining revealed an increase in the population of cells at the sub-G1 stage and apoptotic morphological changes in the nucleus. The oncology array identified 84 oncology-related proteins and a suppressed expression of Bcl-xL and survivin. Western blotting showed that PNU-74654 could interfere with cell cycle-related proteins through the NF-κB pathway. : PNU-74654 shows antiproliferative and antimigration effects against HepG2 and Huh7 cells, and its antitumor activity may be attributable to its interference in cell cycle regulation and the NF-κB pathway.
PNU-74654 是一种 Wnt/β-连环蛋白抑制剂，已被报道具有抗肿瘤活性；然而，PNU-74654 在肝细胞癌 (HCC) 中的治疗潜力尚未得到详细研究。本研究旨在阐明 PNU-74654 对 HCC 的细胞毒性作用，并揭示其分子机制。
选择 HepG2 和 Huh7 肝癌细胞系来确定 PNU-74654 的抗肿瘤特性。通过细胞活力测定法评估肝癌细胞对 PNU-74654 的存活情况，通过流式细胞术分析 PNU-74654 的凋亡作用，并通过 Hoechst 染色进行可视化。使用肿瘤学阵列探索 PNU-74654 在细胞中作用的潜在分子途径。通过划痕愈合试验检查迁移特性，并进行 Western blot 以评估蛋白表达。
用 PNU-74654 处理可降低细胞活力并抑制细胞迁移。细胞周期分析和 Hoechst 染色显示，亚 G1 期细胞群增加，细胞核出现凋亡形态变化。肿瘤学阵列鉴定了 84 种肿瘤相关蛋白，Bcl-xL 和 survivin 的表达受到抑制。Western blot 显示，PNU-74654 可以通过 NF-κB 途径干扰细胞周期相关蛋白。
PNU-74654 对 HepG2 和 Huh7 细胞表现出增殖抑制和迁移抑制作用，其抗肿瘤活性可能归因于其对细胞周期调控和 NF-κB 途径的干扰。
