摘要
目的探讨G蛋白偶联雌激素受体GPER特异性拮抗剂G15对子宫内膜癌细胞Ishikawa、HEC-1A、KLE侵袭、迁移的影响及相关作用机制。方法应用划痕愈合及Transwell迁移、侵袭实验检测不同浓度G15作用不同时间对子宫内膜癌细胞Ishikawa、HEC-1A、KLE迁移能力的影响。应用Western blotting检测Ishikawa、HEC-1A、KLE细胞中GPER、MMP9及ERK蛋白表达水平的变化。结果划痕愈合实验及Transwell小室实验显示,随着G15浓度的增加和作用时间的延长,经E2处理的HEC-1A、KLE细胞迁移能力逐渐增强,而G15对经E2处理的Ishikawa细胞迁移能力的抑制作用较弱。Western blotting结果显示,G15可显著抑制E2诱导的HEC-1A、KLE细胞GPER、ERK、MMP9蛋白表达上调。而在Ishikawa细胞中,G15仅能抑制GPER的表达,对ERK、MMP9蛋白的表达无显著影响。结论G15可抑制经E2处理的子宫内膜癌细胞Ishikawa、HEC-1A、KLE的迁移能力,且对ER低表达HEC-1A细胞和ER阴性KLE细胞迁移能力的抑制作用更为显著,而GPER/ERK/MMP9信号通路在这一过程中发挥重要作用。因此,GPER特异性拮抗剂G15有望成为子宫内膜癌新型靶向治疗药物。
Objective To investigate the effects of GPER specific antagonist G15 on invasion and migration of endometrial cancer cells Ishikawa,HEC-1A,KLE,and to analyze the related mechanism.Methods The scratch wound healing and Transwell migration experiments were used to detect the changes in the invasion and migration ability of the three types of cells after treatment of different concentrations of G15.Western blotting was performed to detect the changes of GPER,MMP9 and ERK protein expression.Results Scratch wound healing experiment and Transwell migration experiment showed that G15 inhibited the migration of E2-treated HEC-1A and KLE cells in a concentration and time-dependent way,while G15 had a weaker inhibition effect on migration ability of E2-treated Ishikawa cells.Western blotting results showed that G15 inhibited the E2-mediated up-regulation of GPER,ERK and MMP protein significantly in HEC-1A and KLE cells.In contrast,in Ishikawa cells,G15 down-regulated the expression of GPER,but had no effect on ERK and MMP9 protein.Conclusion G15 has inhibitory effects on the E2-mediated migration of endometrial cancer cells Ishikawa,HEC-1A and KLE,and more evident inhibitory effects in HEC-1A and KLE cells.The GPER/ERK/MMP9 signal pathway plays an important role in this process.Therefore,GPER specific antagonist G15 may have the potential to serve as a new drug for targeted therapy for endometrial cancer.
作者
卢杰红
赵焕焕
徐娟
张春丽
邵校
张舒
李利
LU Jiehong;ZHAO Huanhuan;XU Juan;ZHANG Chunli;SHAO Xiao;ZHANG Shu;LI Li(The 4th Hospital of Hebei Medical University,Shijiazhuang,Hebei,050011,China)
出处
《肿瘤药学》
CAS
2021年第6期693-700,共8页
Anti-Tumor Pharmacy
基金
医学科学研究重点课题计划及政府资助临床医学优秀人才培养和基础课题研究项目(20170712)。
