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对药物偶联后的肝癌特异性黏附肽进行体外靶向效果评价,并开展初步的药效学研究。将与阿霉素偶联的肝癌特异性黏附肽A54和突变对照肽A54M分别作用于肝癌细胞株BEL-7402,通过细胞活性检测、荧光观察、流式细胞仪分析以及细胞存活实验,对阿霉素偶联药物的靶向杀伤效果及作用机制进行研究。结果:与对照组相比,DOX-A54(doxorubicinconjugated peptide A54)处理后肿瘤细胞的活性明显降低。荧光显微镜观察发现,相同处理时间后,DOX-A54组的细胞核内阿霉素富集程度与对照组相比明显提高。此外,细胞凋亡和细胞存活实验表明新型免疫毒素对肝癌细胞的毒性作用主要是通过导致细胞坏死而非促进细胞凋亡产生的。研究提示,这种偶联阿霉素的肝癌特异性黏附肽在体外对肝癌细胞有一定的靶向杀伤作用,具有潜在的应用前景。
Hepatoma specific adhesion peptide after drug conjugation was evaluated in vitro and preliminary pharmacodynamic studies were carried out. The hepatocarcinoma-specific adhesion peptide A54 and the mutant control peptide A54M conjugated with doxorubicin were respectively applied to the hepatocellular carcinoma cell line BEL-7402. The cell viability assay, fluorescence observation, flow cytometry analysis, Targeted cytotoxicity and its mechanism of action. Results: Compared with the control group, the activity of DOX-A54-treated tumor cells was significantly decreased. Fluorescence microscopy showed that after the same treatment time, the concentration of adriamycin in the nucleus of DOX-A54 group was significantly increased compared with the control group. In addition, apoptosis and cell survival experiments show that the new immunotoxins on liver cancer cells toxicity mainly through the cause of cell necrosis rather than promote apoptosis. The research suggests that this hepatocarcinoma-specific adhesion peptide coupled with doxorubicin has certain targeted killing effect on liver cancer cells in vitro, and has potential application prospect.