摘要
目的从8个YN33系列表皮生长因子受体(EGFR)蛋白酪氨酸酶抑制剂中筛选具有抗肿瘤活性的化合物,并进一步评价其在体外的抗肿瘤效果。方法首先采用体外激酶实验对YN33系列化合物进行初步筛选,观察它们对EGFR蛋白酪氨酸酶的抑制作用;采用MTS法观察筛选出的活性化合物在体外对人表皮癌A431细胞株、人胃癌N87细胞株和人乳腺癌BT474细胞株的增殖抑制作用,以及体外筛选出的YN33-5化合物对人正常胚肺成纤维MRC-5细胞增殖的抑制作用。结果激酶实验结果,发现4个具有抑制EGFR活性的化合物:YN33-3,YN33-5,YN33-6,YN33-8。YN33-5对A431、BT474、N87细胞株的半数抑瘤浓度(IC50)分别为:(9.743 3±2.795 9)μmol/L,(4.611 7±2.222 5)nmol/L和(44.048 3±21.793 1)nmol/L,抑制效应呈剂量依赖性。结论 YN33-5具有较好抗肿瘤活性,可抑制多种肿瘤细胞的增殖。
Objective To screen 8 series of YN33 compounds,which are EGFR tyrosine kinase inhibitors,and evaluate their anti-tumor effect in vitro.Methods Preliminary screening was carried out by detecting the EGFR kinase phosphorylation inhibition activity of the compounds.MTS assay was adopted for secondary anti-tumor screen of the selected compounds using A431,N87 and BT474 cell lines in vitro.And we investigated the influence caused by the screened compound YN33-5 in normal cells,MTS assay was carried out in MRC-5 cell line as well.Results According to the kinase assay,4 compounds were selected,which were YN33-3,YN33-5,YN33-6,and YN33-8.The IC50 of YN33-5 in inhibition of A431,BT474 and N87 cell lines proliferation in vitro was（9.743 3±2.795 9）μmol/L,（4.6117±2.222 5）nmol/L and（44.048 3±21.793 1）nmol/L,and the inhibition effect were dose-dependent.Conclusion YN33-5 is probably an effective EGFR tyrosine kinase inhibitor with significant anti-tumor activity.
出处
《重庆医学》
CAS
CSCD
北大核心
2012年第33期3498-3500,共3页
Chongqing medicine
基金
国家科技部重大专项(010ZX09401-306-1-1)
关键词
受体
表皮生长因子
抗肿瘤活性
MTS法
recetptor
epidermal growth factor
anti-tumor activity
MTS assay
