| 邢 雪,陈凡平,刘真一,王 燕,甘加宽,李双奎,张 明,李哲萍.大黄酸调节Ras/ERK信号通路对肝细胞癌细胞增殖、迁移和侵袭的影响[J].,2024,(2):240-246 |
| 大黄酸调节Ras/ERK信号通路对肝细胞癌细胞增殖、迁移和侵袭的影响 |
| Effects of Rhein on Proliferation, Migration and Invasion of Hepatocellular Carcinoma Cells by Regulating Ras/ERK Signaling Pathway |
| 投稿时间：2023-07-03 修订日期：2023-07-27 |
| DOI：10.13241/j.cnki.pmb.2024.02.007 |
| 中文关键词: 大黄酸 Ras/ERK信号通路 肝细胞癌 增殖 迁移 侵袭 |
| 英文关键词: Rhein Ras/ERK signaling pathway Hepatocellular carcinoma Proliferation Migration Invasion |
| 基金项目:河北省中医药管理局科研计划项目（2022368） |
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| 中文摘要: |
| 摘要 目的：探讨大黄酸调节大鼠肉瘤蛋白（Ras）/胞外信号调控激酶（ERK）信号通路对肝细胞癌（HCC）细胞增殖、迁移和侵袭的影响。方法：使用不同浓度（0、12.50、25、50、100、150、200 mol/L）大黄酸处理HepG2细胞，检测细胞活性，筛选最佳大黄酸浓度。将细胞分为对照组、大黄酸低、中、高浓度组、大黄酸高浓度+Ras/ERK激活剂组（大黄酸高浓度+ML-099组），分别检测各组细胞集落形成数、划痕愈合率、细胞侵袭数和Ras、p-ERK、ERK蛋白表达。结果：大黄酸以浓度和时间依赖性降低HepG2细胞活性（P<0.05），选用25、50、100 mol/L处理HepG2细胞24 h用于后续实验；与对照组比较，大黄酸低、中、高浓度组细胞集落形成数、G0/G1细胞比例、细胞划痕愈合率、细胞侵袭数和原癌基因（c-Myc）、细胞周期蛋白D1（CyclinD1）、Ras、p-ERK/ERK蛋白表达呈浓度依赖性降低，S期和G2/M细胞比例、p53蛋白表达呈浓度依赖性增加（P<0.05）；与大黄酸高浓度组比较，大黄酸高浓度+ML-099组细胞集落形成数、G0/G1细胞比例、细胞划痕愈合率、细胞侵袭数和c-Myc、CyclinD1、Ras、p-ERK/ERK蛋白表达显著增加，S期和G2/M细胞比例、p53蛋白表达显著降低（P<0.05）。结论：大黄酸可能通过抑制Ras/ERK信号通路抑制HCC细胞增殖、迁移和侵袭。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effects of rhein on the proliferation, migration and invasion of hepatocellular carcinoma (HCC) cells by regulating rat sarcoma protein (Ras)/ extracellular signal-regulated kinase (ERK) signaling pathway. Methods: HepG2 cells were treated with different concentrations (0, 12.50, 25, 50, 100, 150, 200 mol/L) of rhein to detect cell activity and screen the best concentration of rhein. The cells were divided into control group, low, medium and high concentration rhein group, high concentration rhein+Ras/ERK activator group (high concentration rhein+ML-099 group), the number of cell colony formation, scratch healing rate, the number of cell invasion and the expression of Ras, p-ERK and ERK protein were detected in each group. Results: Rhein reduced the activity of HepG2 cells in a concentration-and time-dependent manner (P<0.05), HepG2 cells were treated with 25, 50, 100 mol/L for 24 h for subsequent experiments. Compared with control group, the number of cell colony formation, the proportion of G0/G1 cells, cell scratch healing rate, the number of cell invasion and the expression of proto-oncogene (c-Myc), cyclin D1 (CyclinD1), Ras and p-ERK/ERK protein in low, medium and high concentration groups of rhein decreased in a concentration-dependent manner, and the proportion of S phase and G2/M cells and the expression of p53 protein increased in a concentration-dependent manner (P<0.05). Compared with rhein high concentration group, the number of cell colony formation, the proportion of G0/G1 cells, cell scratch healing rate, the number of cell invasion and the expression of c-Myc, CyclinD1, Ras and p-ERK/ERK protein in rhein high concentration+ML-099 group were significantly increased, and the proportion of S phase and G2/M cells and the expression of p53 protein were significantly decreased (P<0.05). Conclusion: Rhein may inhibit the proliferation, migration and invasion of HCC cells by inhibiting the Ras/ERK signaling pathway. |
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