首页> 中文期刊> 《浙江医学》 >肝素酶B细胞表位MAP疫苗对肝癌生长及肺转移影响的实验研究

肝素酶B细胞表位MAP疫苗对肝癌生长及肺转移影响的实验研究

         

摘要

Objective To investigate the effect of MAP vaccine based on B cel epitopes of heparanase on primary hepa-tocel ular carcinoma and its mechanism. Methods Rabbits were immunized with the freshly synthesized MAP vaccine to obtain specific antibodies. Tumor- bearing murine model of orthotopic implants with human hepatocel ular carcinoma HCC- 97H cel s were established in BALB/c nude mice, and the vaccine- derived polyclonal antibodies were injected in tumor- bearing nude mice. The tumor growth, pulmonary metastasis and the expression of VEGF, bFGF and CD34 in hepatoma tissues were evaluated and analyzed. Results After active immunity using the B- lymphocyte MAP vaccine of human heparanase, the specific antibod-ies of high titer were harvested. Both the pulmonary metastatic foci and the orthotopic HCC volumes and the expression of VEGF, bFGF and CD34 (MVD) in experimental groups treated with anti- MAP antibodies were much lower than those in negative control group (P<0.01) or positive control group (P<0.05) in a certain dose- dependent manner. Conclusion This study suggests that the synthesized MAP vaccine based on B- cel epitopes of human heparanase is capable of attenuating human HCC growth and metastasis in nude mice.%目的:研究自行合成的肝素酶B细胞表位多抗原肽(MAP)疫苗在活体内对HCC97H原发性肝癌生长及肺转移的抑制作用。方法新鲜合成肝素酶B淋巴细胞表位MAP疫苗并经主动免疫白毛黑眼兔获得特异性免疫血清,经纯化后被动免疫于荷瘤鼠体内,观察肝癌局部生长侵袭情况及肺部微转移灶数目、肝癌组织中VEGF、bFGF、CD34的表达等情况,并进行统计分析。结果通过主动免疫的方法,获得了含高浓度、高纯度且能与肝素酶50kDa大亚基及前体蛋白特异性结合的抗MAP抗体的免疫血清,该特异性抗体可显著抑制HCC97H细胞肝素酶活性、抑制VEGF和bFGF的表达及降低微血管密度;注射抗肝素酶B细胞表位MAP抗体各组的原位肝癌体积及肺转移灶数目都明显小于未经免疫兔IgG对照组(P<0.01)及希罗达阳性对照组(P<0.05),且其作用具有一定的浓度依赖性。结论本研究证实了肝素酶B淋巴细胞表位MAP疫苗在活体内具有抗原发性肝癌生长及抑制肺转移的作用,可为原发性肝癌的防治提供新的思路。

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