摘要
目的:研发针对中国南方和东南亚高发恶性肿瘤鼻咽癌的新型靶向抗癌药。方法:用本课题组合成的一种新型吲哚满酮类化合物IF239处理培养的鼻咽癌细胞系(CNE),酸性磷酸酶法测定化合物IF239对CNE细胞百分活率的影响;光学显微镜下观察细胞形态变化和黏附状态的改变;流式细胞术检测细胞周期时相的改变;Wes-tern blot检测细胞周期关键调控分子的变化。结果:IF239对CNE细胞具有强大的杀伤作用,其抗肿瘤机制可能与抑制细胞黏附和诱导细胞周期阻滞于G2/M期有关;而G2/M期阻滞与IF239上调cyclin B1和细胞周期蛋白依赖激酶1(CDK1)磷酸化水平有关。结论:IF239对CNE细胞的增殖抑制作用显著,其作用机制独特,具有潜在应用前景。
Objective：To develop novel targeted anticancer medicines for effective treatment of nasopharyngeal carcinoma（NPC）,a prevalent malignant disease in southern China and southeast Asia.Methods： CNE cells were treated with a novel indolinone IF239 synthesized by our research group.Cell viability was determined by the acid phosphatase assay（APA）.Morphologic changes and adhesion status of CNE cells treated with IF239 were observed under a light microscope.Flow cytometry was used to analyze the cell cycle phases.Key regulating molecules in the cell cycle progression were detected by Wes-tern blotting.Results： IF239 had potent cytotoxic effect on CNE cells.The possible antitumor mechanisms of IF239 involved inhibition of cell adhesion and cell cycle arrest in the G2/M phase.Moreover,G2/M arrest caused by IF239 was related to up-regulation of both cyclin B1 and the phosphorylation level of CDK1.Conclusion： IF239 has high anticancer activity over CNE cells,and has unique anticancer mechanisms,suggesting that IF239 has promising application potentials.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2009年第6期640-644,共5页
Journal of Peking University:Health Sciences
基金
国家自然科学基金项目(30570413)资助~~
关键词
抗肿瘤药
鼻咽肿瘤
细胞周期
细胞黏附
Antineoplastic agents
Nasopharyngeal neoplasms
Cell cycle
Cell adhesion
