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目的:评价EGFR抑制剂4-取代-7氯喹啉衍生物(TW9183)的体内外抗肿瘤生物活性。方法:采用分子对接技术探讨其与EGFR之间的相互作用模式,蛋白免疫印迹法评价在蛋白水平的直接作用,体外细胞生物学及体内裸鼠移植瘤模型探讨TW9183的活性。结果:EGFR受体的氨基酸残基MET769,PRO770,LYS721可与TW9183间形成氢键,蛋白印免疫迹法表明化合物抑制EGFR的磷酸化;体外细胞实验显示TW9183有明显抑制食管癌细胞增殖、周期阻滞于G2/M期及促进凋亡的效果;裸鼠食管癌移植瘤模型验证其在体内同样具有抑制肿瘤生长促进凋亡的作用。结论:TW9183在体内外实验中显示具有潜在的抗食管癌作用。
AIM: To evaluate in vitro and in vivo antitumor biological activity of the EGFR inhibitor 4-substituted-7-chloroquinoline derivative (TW9183). METHODS: The molecular docking technique was used to investigate the interaction between TW9183 and EGFR, the direct effect of protein immunoblotting on protein level, the cell biology in vitro and the in vivo nude mouse xenograft model. Results: The amino acid residues MET769, PRO770 and LYS721 of EGFR receptor could form hydrogen bonds with TW9183. Western blotting showed that the compounds inhibited EGFR phosphorylation. In vitro experiments showed that TW9183 could significantly inhibit the proliferation of esophageal cancer cells, G2 / M phase arrest and promote apoptosis; nude mice model of esophageal cancer xenografts in vivo inhibition of tumor growth also has the role of promoting apoptosis. Conclusion: TW9183 showed a potential anti-esophageal cancer effect in vitro and in vivo.