四氢异喹啉类新化合物SYT-1抑制肿瘤细胞增殖的机制

Mechanism of inhibiting proliferation of tumor cells by a new tetrahydroisoquinoline compound SYT-1

探讨四氢异喹啉类新化合物SYT-1对肿瘤细胞增殖抑制作用及其机制。采用CCK-8(cell counting kit-8)法检测细胞增殖;克隆形成实验检测细胞克隆形成能力;JC-1探针法检测细胞线粒体膜电位;DCFH-DA(2',7'-dichlorodihydrofluorescein diacetate)探针法检测细胞内活性氧水平;Annexin V-FITC/PI(fluorescein isothiocyanate/propidium)复染法检测细胞凋亡;Western blot法检测相关蛋白表达水平。实验结果表明,SYT-1对6种人源癌细胞的增殖具有显著抑制作用,其中对乳腺癌MCF-7细胞的抑制作用最强,半数抑制浓度(half maximal inhibitory concentration,IC_(50))为5.87μmol·L^(-1),优于顺铂(IC_(50)为8.92μmol·L^(-1))。进一步研究表明,SYT-1可剂量依赖性抑制MCF-7细胞的单克隆形成能力,并能引起细胞线粒体膜电位下降和活性氧水平升高。此外,SYT-1可以显著抑制PI3K-Akt(phosphatidylinositol 3-kinase/protein kinase B)信号通路的激活并诱导MCF-7细胞的凋亡。上述研究结果表明,作为一种新型四氢异喹啉类化合物,SYT-1具有抑制肿瘤细胞增殖的潜力。

In this study,we investigated the inhibitory effect of SYT-1,a new compound of tetrahydroisoquinoline,on tumor cell proliferation and underlying mechanisms.Cell counting kit-8(CCK-8)method was used to detect cell proliferation;clone formation experiment was used to detect cell clone formation ability;JC-1 probe was used to detect cell mitochondrial membrane potential;2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)probe was used to detect intracellular reactive oxygen species;Annexin V-FITC/PI(fluorescein isothiocyanate/propidium)counterstaining method was used to detect apoptosis;Western blot assay was used to detect the expres‐sion level of related proteins.The experimental results show that SYT-1 has a significant inhibitory effect on the proliferation of six human-derived cancer cells.Among them,the inhibitory effect on breast cancer MCF-7 cells is the strongest,the half maximal inhibitory concentration(IC_(50))of SYT-1 of 48 h administration on MCF-7 cells is 5.87μmol·L^(-1),which is better than that of cisplatin(8.92μmol·L^(-1)).Further studies have shown that SYT-1 can dose-dependently inhibit the monoclonal formation ability of MCF-7 cells,and can cause the mitochondrial mem‐brane potential of the cells to decrease and the level of reactive oxygen species to increase.In addition,SYT-1 can significantly inhibit the activation of PI3K-Akt(phosphatidylinositol 3-kinase/protein kinase B)signaling pathway and induce apoptosis of MCF-7 cells.The above research results show that,as a new type of tetrahydroisoquinoline compound,SYT-1 has the potential to inhibit tumor cell proliferation.