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本研究旨在探讨β-岚香酮酸(β-elemonic acid, β-EA)对肝细胞癌(hepatocellular carcinoma, HCC)细胞增殖和凋亡的影响及其作用机制。利用CCK8法检测β-EA对人HCC细胞Huh7和PLC/PRF/5活力的影响；利用Annexin V-FTTC/7AAD染色检测细胞凋亡变化；利用流式细胞周期检测β-岚香酮酸对HCC细胞周期的影响；利用Western blot检测凋亡相关蛋白Bcl2、 BAX、 cleaved-caspase 3和细胞周期相关蛋白CDK1、 Cyclin B1的表达。结合网络药理学预测β-EA抑制HCC细胞增殖的分子机制，检测PI3K/AKT信号通路蛋白的表达。通过构建H22皮下移植瘤模型，体内证实了β-EA对HCC的生长抑制作用。结果表明，β-EA能够显著抑制Huh7和PLC/PRF/5细胞活力，诱导HCC细胞凋亡和G2/M期细胞阻滞，上调促凋亡蛋白cleaved-caspase 3、 BAX,下调抗凋亡蛋白Bcl2、细胞周期蛋白Cyclin B1、细胞周期依赖性激酶CDK1、 p-PI3K、 p-AKT的表达。皮下移植瘤模型证实β-EA能够有效降低瘤重、瘤体积和Ki67的表达。本研究结果表明β-EA能够通过PI3K/AKT信号通路诱导HCC细胞凋亡和G2/M期细胞阻滞。
Abstract：The aim of this study was to investigate the effect of β-elemonic acid(β-EA) on hepatocellular carcinoma(HCC) proliferation and apoptosis and its mechanism.CCK8 assay was used to detect the effects of β-EA on the cell viability of human HCC cells Huh7 and PLC/PRF/5. Annexin V-FTTC/7AAD staining was used to detect cell apoptosis. The effect of β-EA on cell cycle of HCC cells was detected by flow cytometry. The expressions of apoptosis-related proteins Bcl2, BAX, cleaved-caspase 3 and cell cycle related proteins CDK1 and Cyclin B1 were detected by Western blot. The molecular mechanism of β-EA inhibiting the proliferation of HCC cells was predicted by network pharmacology, and the protein expression of PI3K/AKT signaling pathway was detected. The growth inhibition effect of β-EA on HCC was confirmed by constructing H22 subcutaneous transplantation tumor model in vivo. The results showed that β-EA significantly inhibited Huh7 and PLC/PRF/5 cell viability, induced cell apoptosis and G2/M cell arrest. The expression of pro-apoptotic protein cleaved-caspase 3 and BAX was up-regulated, and the expression of anti-apoptotic protein Bcl2, cell cycle protein Cyclin B1, cycle-dependent kinases CDK1, p-PI3K, and p-AKT was down-regulated. The subcutaneous tumor transplantation model confirmed that β-EA can effectively reduce tumor weight, tumor volume, and Ki67 expression. The results of this study suggest that β-EA can induce apoptosis and G2/M cell arrest of HCC cells through PI3K/AKT signaling pathway.
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基本信息:
DOI：10.13417/j.gab.043.000907
中图分类号:R735.7
引用信息:
[1]邹晨,乔凤杰,方淼,等.β-岚香酮酸对肝细胞癌细胞增殖和凋亡的影响及其机制[J].基因组学与应用生物学,2024,43(05):907-924.DOI:10.13417/j.gab.043.000907.
基金信息:
国家自然科学基金资助项目(81973773); 上海中医药大学“杏林百人”人才项目; 上海市临床重点专科建设项目(中医专业)(shslczdzk01201); 上海市名老中医学术经验研究工作室(SHGZS-202246); 中医药领军人才项目岐黄学者支持项目共同资助
2023-11-09
2023-11-09
2023-11-09