伊维菌素对人胃癌细胞BGC-823、MGC-803迁移和侵袭的影响及机制研究
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篇名: 伊维菌素对人胃癌细胞BGC-823、MGC-803迁移和侵袭的影响及机制研究
TITLE:
摘要: 目的:研究伊维菌素对人胃癌细胞BGC-823、MGC-803迁移和侵袭能力的影响及其作用机制。方法:0、2.5、5、10、20、40 μmol/L伊维菌素分别作用于BGC-823、MGC-803细胞24 h后用MTT法检测细胞抑制率,再采用Transwell小室侵袭实验观察5     μmol/L伊维菌素和含0.67‰二甲基亚砜的磷酸盐缓冲液(对照组)作用24 h对BGC-823、MGC-803细胞迁移和侵袭的影响,Western blot法分别检测5、10 μmol/L伊维菌素和含0.67‰二甲基亚砜的磷酸盐缓冲液(对照组)作用于BGC-823、MGC-803细胞24 h后上皮-间质转化(EMT)标记物E-cadherin、N-cadherin、Vimentin、Snail和EMT转导通路转化生长因子β(TGF-β)/Smad中TGF-β1、TGF-βR、Smad2、Smad3 蛋白的表达水平。结果:伊维菌素对BGC-823、MGC-803细胞生长均有抑制作用,其细胞抑制率与其浓度呈正相关。与对照组比较,5 μmol/L伊维菌素作用后BGC-823、MGC-803细胞的迁移数和侵袭数均明显减少(P<0.01或P<0.001);5、10 μmol/L伊维菌素作用后BGC-823、MGC-803细胞中E-cadherin蛋白表达明显增强(P<0.05或P<0.01或P<0.001),N-cadherin、Vimentin、Snail、TGF-βR、Smad2、Smad3蛋白表达均明显减弱(P<0.05或P<0.01或P<0.001),TGF-β1蛋白仅在10    μmol/L伊维菌素作用后明显减弱(P<0.05)。结论:伊维菌素能显著抑制BGC-823、MGC-803细胞的迁移和侵袭,其可能与抑制TGF-β/Smad活性从而影响EMT过程有关。
ABSTRACT: OBJECTIVE: To study the effects of ivermectin on the migration and invasion of human gastric cancer cell lines BGC-823 and MGC-803 and its mechanism. METHODS: After treated with 0, 2.5, 5, 10, 20, 40 μmol/L ivermectin for 24 h, inhibitory rate of human gastric cancer cell lines BGC-823 and MGC-803 were detected by MTT assay. Effects of 5 μmol/L ivermectin and phosphate buffercontaining 0.67‰ dimethyl sulfoxide (control group) for 24 h on the migration and invasion of` gastric cancer cells BGC-823 and MGC-803 were observed by Transwell chamber invasion assay.Western blot assay was used to detect the protein expression of TGF-β1, TGF-βR, Smad2 and Smad3 in epithelial-mesenchymal transition (EMT) markers E-cadherin, N-cadherin, Vimentin, Snail and EMT transduction pathway TGF-β/smad of BGC-823 and MGC-803 cells after treated with 5, 10 μmol/L ivermectin and phosphate buffercontaining 0.67‰ dimethyl sulfoxide (control group) for 24 h. RESULTS: Ivermectin could inhibit the growth of BGC-823 and MGC-803, inhibitory rate of it was positively correlated with its concentration. Compared with control group, the number of migration and invasion BGC-823 and MGC-803 cells were decreased significantly after treated with 5 μmol/L ivermectin (P<0.01 or P<0.001); the expression of E-cadherin protein was enhanced significantly in BGC-823 and MGC-803 cells after treated with 5 and 10 μmol/L ivermectin (P<0.05 or P<0.01 or P<0.001); the protein expression of N-cadherin, Vimentin, Snail, TGF-βR, Smad2 and Smad3 were decreased significantly (P<0.05, P<0.01 or P<0.001); protein expression of TGF-β1 was decreased significantly after treated with 10 μmol/L ivermectin (P<0.05). CONCLUSIONS: Ivermectin can significantly inhibit the migration and invasion of gastric cancer cells BGC-823 and MGC-803, and inhibiting the biological activity of EMT by reducing the expression of TGF-β/smad pathway is one of the mechanisms that inhibit the migration and invasion of gastric cancer cells.
期刊: 2019年第30卷第5期
作者: 谢燕娇,邝少轶,邓慧鸣,虞道锐,樊好飞,贾皓,刘嫱
AUTHORS: XIE Yanjiao,KUANG Shaoyi,DENG Huiming,YU Daorui,FAN Haofei,JIA Hao,LIU Qiang
关键字: 伊维菌素;人胃癌细胞BGC-823;人胃癌细胞MGC-803;转化生长因子β/Smad;细胞迁移;细胞侵袭
KEYWORDS: Ivermectin; Human gastric cancer cell BGC- 823; Human gastric cancer cell MGC-803; TGF-β/Smad; Cell migration; Cell invasion
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