Emergency Hospital, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
Chemistry Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
Int J Mol Sci. 2020 Oct 15;21(20):7642. doi: 10.3390/ijms21207642.
The natural flavonoid chrysin possesses antiproliferative activity against various types of cancers, including hepatocellular carcinoma (HCC), which is a common malignancy. However, the exact mechanism of chrysin antiproliferative activity remains unclear. This research was executed to explore the impact of chrysin on glypican-3 (GPC3)/sulfatase-2 (SULF2) axis and lncRNA-AF085935 expression in HCC using HepG2 cells. Cisplatin (20, 50, 100 μg/mL), chrysin (15, 30, and 60 μg/mL) and the combination of 50 μg/mL cisplatin with different concentrations of chrysin were applied for 24/48 h. Cell viability was determined by MTT assay. Protein levels of GPC3 and SULF2 were measured by ELISA at 24/48 h. GPC3 immunoreactivity was detected by immunocytochemistry. Moreover, GPC3 and SULF2 mRNA expressions in addition to lncRNA-AF085935 expression were assessed by qPCR at 48 h. The GPC3 protein, immunostaining and mRNA levels, SULF2 protein and mRNA levels, as well as lncRNA-AF085935 expression, were decreased significantly with cisplatin and chrysin alone when compared with the control untreated HepG2 cells. However, the combination treatment exhibited a better chemopreventive effect in a dose- and time-dependent manner. This study demonstrated, for the first time, the antiproliferative activity of chrysin against HCC through the suppression of the GPC3/SULF2 axis along with the downregulation of lncRNA-AF085935 expression. Synergistic effect of chrysin with cisplatin could potentiate their antiproliferative action in a dose- and time-dependent manner.
天然黄酮 chrysin 对包括肝癌 (HCC) 在内的多种癌症具有抗增殖活性，HCC 是一种常见的恶性肿瘤。然而，chrysin 抗增殖活性的确切机制尚不清楚。本研究旨在通过 HepG2 细胞探索 chrysin 对 GPC3/SULF2 轴和 lncRNA-AF085935 表达的影响。采用顺铂 (20、50、100μg/ml)、chrysin(15、30 和 60μg/ml)以及 50μg/ml 顺铂与不同浓度 chrysin 的联合作用，作用 24/48h。MTT 法测定细胞活力。24/48h 时用 ELISA 法测定 GPC3 和 SULF2 蛋白水平。免疫细胞化学法检测 GPC3 免疫反应性。此外，48h 时用 qPCR 检测 GPC3 和 SULF2mRNA 表达以及 lncRNA-AF085935 表达。与未处理的 HepG2 细胞相比，单独使用顺铂和 chrysin 可显著降低 GPC3 蛋白、免疫染色和 mRNA 水平、SULF2 蛋白和 mRNA 水平以及 lncRNA-AF085935 表达。然而，联合治疗以剂量和时间依赖的方式表现出更好的化学预防作用。本研究首次证明，chrysin 通过抑制 GPC3/SULF2 轴以及下调 lncRNA-AF085935 表达来抑制 HCC 的增殖活性。chrysin 与顺铂的协同作用可以增强它们在剂量和时间依赖性方面的抗增殖作用。
