整合素αvβ_3拮抗剂-苯丁酸氮芥偶联毒素的合成及其体外抗肿瘤活性

目的合成整合素(Integrin)αvβ3拮抗剂-苯丁酸氮芥偶联毒素,并检测其体外抗肿瘤活性。方法化学合成In-tegrinαvβ3拮抗剂,并与苯丁酸氮芥通过酰胺键偶联,MTT法检测偶联毒素对人脐静脉内皮细胞ECV304和肝癌细胞HepG2的抑制作用。结果合成的偶联毒素经核磁共振和质谱分析鉴定,表明结构正确,纯度达90%以上,对HepG2细胞的抑制效果弱于苯丁酸氮芥,但对ECV304细胞的抑制特异性较好。结论Integrinαvβ3拮抗剂-苯丁酸氮芥偶联毒素可抑制HepG2和ECV304细胞的增殖,为癌症治疗提供了一个新途径。

Synthesis and In Vitro Antitumor Antactivity of Integrin αvβ_3 Antagonist-Chlorambucil Conjugate Toxin

Objective To synthesize integrin αvβ3 antagonist-chlorambucil conjugate toxin and determine its in vitro antitumor activity. Methods Synthesize integrin αvβ3 antagonist chemically and conjugate to chlorambucil through a amido bond. Determine the inhibitory effect of the conjugate toxin on human umbilical vein endothelial cells ECV304 and liver cancer HepG2 cells by MTT method. Results Nuclear magnetic resonance and mass spectrography showed correct structure of the synthetic conjugate toxin. The conjugate toxin reached a purity of more than 90%, and its inhibitory effect on HepG2 cells was weaker than that of chlorambucil. However, it showed highly specific inhibitory effect on ECV304 cells. Conclusion The synthetic integrin αvβ3 antagonist-chlorambucil conjugate toxin inhibited the proliferation of HepG2 and EVC304 cells, which provided a novel route for therapy of tumors.