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机构地区:[1]上海交通大学附属胸科医院药剂科,上海200030 [2]复旦大学上海医学院分子生物学实验室,上海200032 [3]复旦大学附属中山医院肝癌研究所,上海200032
出 处:《药学服务与研究》2008年第5期332-335,共4页Pharmaceutical Care and Research
基 金:国家高技术研究发展计划(863计划)(No.2004AA215201);上海市现代生物与新药产业发展基金项目(No.024319212)
摘 要:目的:观察多聚β肽及其聚乙二醇(PEG)修饰物对肝癌细胞株侵袭黏附能力和对裸鼠移植人肝癌早期切除术后转移复发的影响。方法:以MTT法测量多聚β肽和其PEG修饰物对肝癌细胞与纤连蛋白(FN)黏附的影响。以细胞侵袭实验观察多聚β肽及其PEG修饰物对肝癌细胞侵袭能力的影响。以LCI-D20裸鼠人肝癌转移模型为材料,观察多聚β肽及其PEG修饰物对早期肝癌切除术后转移复发的影响。结果:β2、β2-PEG、β3和β3-PEG对SMMC-7721细胞与FN黏附抑制率分别为31.3%、39.2%、45.7%和57.1%,侵袭抑制率分别为33.6%、35.9%、38.3%和41.2%;对HCCLM6细胞与FN的黏附抑制率分别为48.7%、60.9%、63.4%和79.3%,侵袭抑制率分别为36.8%、46.6%、45.6%和50.8%。多聚β肽及其PEG修饰物组切缘复发肿瘤重量和肺转移灶个数显著低于对照组(P<0.05)。结论:多聚β肽及其PEG修饰物能抑制肿瘤细胞的黏附和侵袭能力,亦能防治裸鼠移植人肝癌早期切除术后的转移和复发。Objective: To study the inhibitory effect of poly-β peptide and the products of pegylation(PEG-poly-β peptides) on adhesion and invasion ability of liver cancer cell line and their preventive effect on liver cancer recurrence and metastasis after liver cuncer resection in a nude mouse model. Methods: The influence of poly-β peptide and PEG-poly-β-peptides on the adhesion of tumor cell(SMMC-7721, HCCLM6) to fihronectin(FN) was studied by MTT method, and their influence on invasion ability of tumor cell was observed by cell invasion experiment. LCI-D20 human liver cancer metastasis model was used to observe the effect of poly-β peptide and PEG-poly-β peptides on recurrence and metastasis of liver cancer in nude mice. Results: The 4 kinds of peptides(β2,β2-PEG,β3,β3-PEG) could inhibit the adhesion of SMMC 7721 and HCCLM6 tumor cells to FN specifically. The inhibitory effect of pegylated polypeptides on the adhesion was stronger than that of polypeptides(P〈0.05). The invasion ability of HCCLM6 and SMMC-7721 tumor cells were inhibited obviously by β2 , β2-PEG,β3 and β3-PEG. For HCCLM6 tumor cells, the inhibitory rates of invasion were 36.8% ,46.6% ,45.6% and 50.8% by β2,β2 PEG,β3 and β3-PEG, respectively. For SMMC-7721 tumor cells, the inhibitory rates of invasion were 33.6%,35.9% ,38.3%and 41.2% by β2, β2 PEG,β3 and β3 PEG, respectively. The poly-β peptides and PEG-poly-β-peptides could decrease the weight of recurrent tumor at incisal margin and the number of lung metastatic loci ohviously(P〈0.05). Conclusion: The poly-β peptides and PEG-poly-β- peptides can inhibit the adhesion and invasion ability of tumor cells obviously, and also prevent and inhibit liver cancer metastasis and recurrence.
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