摘要
目的探究新型培美曲塞(PMX)衍生物对A549细胞增殖、迁移及细胞凋亡的影响。方法 MTT法初步筛选12种化合物对A549细胞的细胞毒性,筛选出高活性候选化合物进一步研究其对A549细胞增殖的影响;Transwell细胞迁移实验及划痕愈合实验测定候选化合物对A549细胞迁移的影响;流式细胞术测定候选化合物对A549细胞凋亡的影响。结果初筛发现其中9种化合物对A549细胞增殖具有抑制作用,其中化合物A12抑制作用最为显著,IC_50为(1.26±0.15)μmol/L,且抑制作用存在浓度及作用时间依赖性:IC_50在作用72 h处最低,为(1.06±0.24)μmol/L;Transwell细胞迁移实验及划痕愈合实验结果表明A12能够抑制A549细胞的迁移能力,且抑制作用具有浓度依赖性;流式细胞术实验结果显示A12能够显著提高A549细胞的早期凋亡率(P<0.05)、晚期凋亡坏死率(P<0.01)及总凋亡率(P<0.05)。结论筛选得到的新型PMX衍生物A12能够明显抑制A549细胞的增殖及迁移活性,并能诱导其凋亡。
Objective To detect the effects of new pemetrexed（PMX） derivatives on the proliferation, migration and cell apoptosis of A549 cells. Methods The cytotoxicity of 12 compounds to A549 cells was preliminarily screened by MTT method, and candidate compounds with high activity were selected for further research on the proliferation of A549 cells. Effects of candidate compounds on A549 cells migration were detected by transwell cell migration assay and the wound healing assay. Effects of candidate compounds on the cell apoptosis of A549 cells were detected by flow cytometry. Results The results of preliminary screening of 9 compounds could inhibit the proliferation of A549 cells, with compound A12 the inhibitory effect was the most significant, IC50（1.26 ± 0.15） μmol/L, and the inhibition was concentration and time dependent： the IC50 in the lowest at 72 h was（1.06 ± 0.24） μmol/L; Transwell cell migration assay and the wound healing assay showed that the migration ability of A12 could inhibit A549 cells, and the inhibition was concentration dependent; Flow cytometry results showed that A12 can significantly improve the early apoptosis rate of A549 cells（P 〈 0.05）, late apoptosis and necrosis rate（P 〈 0.01） and total apoptosis rate（P 〈 0.05）. Conclusion The new PMX derivative, A12, could inhibit the proliferation and migration activity of A549 cells and induced apoptosis.
作者
刘秀
贾玉萍
贾庆文
郭中坤
王可洲
卢美超
刘莎
袁栋栋
LIU Xiu;JIA Yu-ping;JIA Qing-wen;GUO Zhong-kun;WANG Ke-zhou;LU Mei-chao;LIU Sha;YUAN Dong-dong
出处
《中国医药生物技术》
2018年第3期226-231,共6页
Chinese Medicinal Biotechnology
基金
国家重点研发计划(2017YFD050160202)
中央引导地方科技发展专项资金项目(CXLC161906)
山东省自然科学基金(ZR2015YL036)
山东省医学科学院医药卫生科技创新工程
