丙泊酚通过调控HDAC1抑制胃癌细胞转移的机制研究

The inhibition mechanism of propofol on gastric cancer metastasis through regulating HDAC1

目的:探讨静脉麻醉药丙泊酚抑制胃癌细胞转移的具体分子机制。方法:不同浓度(1、5、10、20μg/ml)丙泊酚作用MGC-803细胞48h后,MTT实验检测不同浓度丙泊酚细胞增殖的影响,以此选出合适浓度进行下列实验:Transwell实验检测细胞的侵袭和迁移能力;化学比色法检测HDACs总活性;Western blotting实验检测HDAC1、上皮间质转化(EMT)相关蛋白和p38丝裂原激活蛋白激酶(p38 MAPK)通路相关蛋白的表达变化。同时,利用siRNA干扰HDAC1表达后进行上述实验检测相应指标。结果:丙泊酚呈浓度依赖性抑制MGC-803细胞增殖,以影响增殖的较小浓度5μg/ml进行后续实验,丙泊酚处理后侵袭和迁移的细胞数目均明显减少;HDAC1表达和HDACs总活性降低;E-cadherin表达明显上调,N-cadherin、Vimentin、β-catenin、Slug、Snail1表达明显下调;p38蛋白表达无明显变化,p-p38蛋白表达明显减少。siRNA干扰HDAC1表达对MGC-803细胞的作用与丙泊酚一致。结论:丙泊酚可能是通过调控HDAC1表达和下游的p38MAPK通路,抑制胃癌细胞MGC-803的侵袭、迁移和EMT过程。

Objective： To investigate the inhibition molecular mechanism of intravenous anesthetic propofol on gas-tric cancer cells metastasis. Methods：MGC -803 cells were treated with different concentrations （1 jjig/ml,5｜jLg/ml, 10｜jLg/ml,20jjig/ml） of propofol for 48h, and then cell proliferation was determined by MTT assay. An appropriate concentration that had a minimal impact on cell proliferation was confirmed for subsequent experiments. The ability of cell invasion and migration was detected by Transwell experiments. Total HDACs activity was analyzed by chemical colorimetry. Western blotting was used to detect the levels of HDAC1, epithelial mesenchymal transformation （EMT） related proteins,and p38 mitogen - activated protein kinase （MAPK） pathway related proteins. Meanwhile,all the a-bove experiments were carried out similarly in MGC -803 cells after transfection with HDAC1 siRNA. Results ： Propo-fol decreased the ability of cell proliferation in a concentration - dependent manner. Propofol at 5 ｜jig/ml, significantly reduced the amount of invasion and migration cells,total HDACs activity,and the levels of HDAC1. N - cadherin, Vi- mentin,p - catenin, Slug, Snaill, and p - p38 were significantly decreased, and E - cadherin expression was in-creased, while p38 expression had no significant change. Effects of HDAC1 siRNA on MGC - 803 were in accordancewith the effects of propofol. Conclusion ： Propofol inhibits the invasion, migration, and EMT process of gastric cancer cells, through regulating HDAC1 expression and downstream p38 MAPK signaling pathway.