异丙酚通过下调ERK-VEGF/MMP-9信号通路对肝癌细胞增殖、迁移及侵袭的影响及机制研究

Propofol inhibits the proliferation, migration, and invasion of hepatocellular carcinoma cells with down-regulating ERK-VEGF/ MMP-9 signaling pathway

摘要:

目的 探讨异丙酚对人肝癌HepG2细胞增殖、迁移及侵袭多种生物学行为的影响及相关机制。方法 用浓度递增的异丙酚（0 μg/mL、5 μg/mL、10 μg/mL、20 μg/mL）和二甲基亚砜（DMSO）处理HepG2细胞，然后采用体外细胞实验（CCK-8实验、划痕实验、Transwell侵袭实验）检测异丙酚对细胞增殖、迁移及侵袭能力的影响。Western blotting检测HepG2细胞中血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP-9）、细胞外信号调节激酶（ERK）及p-ERK蛋白相对表达量。结果 CCK-8实验结果发现，与空白对照组比较，5 μg/mL组、10 μg/mL组及20 μg/mL组HepG2细胞存活率逐渐降低（P <0.05）。划痕实验结果发现，异丙酚可以有效抑制HepG2细胞的迁移，且随着药物浓度增加细胞迁移能力逐渐减弱（P <0.05）。Transwell侵袭实验结果发现，异丙酚以一种浓度依赖的方式抑制HepG2细胞的侵袭能力（P <0.05）。Western blotting结果发现，异丙酚刺激可降低HepG2细胞中的VEGF、MMP-9及p-ERK/ERK蛋白相对表达量（P <0.05）。结论 异丙酚在体外抑制人肝癌HepG2细胞的增殖、迁移及侵袭，可能与其下调ERK-VEGF/MMP-9信号通路有关。

Abstract:

Objective To investigate the influence of propofol on various biological behaviors such as proliferation, migration, and invasion of HepG2 cells in human liver cancer and related mechanisms.Methods Propofol with increasing concentration (0 μg/mL, 5 μg/mL, 10 μg/mL, and 20 μg/mL) and dimethyl sulfoxide (DMSO) treatment of human liver cancer HepG2 cells, and then in vitro cell assay (CCK-8 assay, Transwell invasion assay, and scratch assay) was used to detect the influence of propofol on cell proliferation, invasion and migration. The protein expressions of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), extracellular signal regulated kinase (ERK), and p-ERK in hepatocellular carcinoma cells were detected with Western blotting.Results The results of CCK-8 found that the viability of HepG2 cells in the 5 μg/mL, 10 μg/mL, and 20 μg/mL groups was gradually reduced compared with the control group (P < 0.05). The results of scratch test showed that propofol could effectively inhibit the migration of HepG2 cells, and the cell migration ability decreased with the increase of drug concentration (P < 0.05). Transwell invasion test found that propofol inhibited the invasion of HepG2 cells in a dose-dependent manner (P < 0.05). Western blotting found that propofol stimulation reduced protein expression of VEGF, MMP-9, and p-ERK/ERK in cells (P < 0.05).Conclusion Propofol inhibits the proliferation, migration, and invasion of hepatocellular carcinoma cell line HepG2 in vitro, which may be related to the down regulation of the ERK-VEGF/MMP-9 signaling pathway.