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热休克蛋白HSP65DNA疫苗抑制黑色素瘤血行转移的实验研究
Study on HSP65 DNA Vaccine in the Hematogenous Metastasis of B16/F10 Melanoma
【摘要】 观察卡介苗来源的热休克蛋白HSP65的DNA疫苗对小鼠B16/F10黑色素瘤血行转移的抑制作用。构建含HSP65编码基因的真核分泌表达DNA疫苗pCR3.1-VS-HSP65及其后融合多个T细胞辅助表位的pCR3.1-VS-HSP65-TP-M2。连续8次肌肉注射免疫C57BL/6J雄性小鼠,采用ELISA法检测小鼠血清中抗HSP65-IgG类抗体滴度,于最后一次免疫后第2周,尾静脉接种B16/F10黑色素瘤细胞,考察该疫苗的免疫原性及药效。ELISA结果显示两种HSP65核酸疫苗均能诱发高滴度抗HSP-IgG类抗体。pCR3.1-VS-HSP65-TP-M2诱发抗体滴度较pCR3.1-VS-HSP65显著增加,并能显著抑制B16/F10的血行转移(P<0.05),且与生理盐水对照组对比抑瘤率达到74.8%(肝),53.2%(肺)。HSP65在增强其免疫原性的基础上能显著抑制B16/F10黑色素瘤的血行转移。
【Abstract】 To observe the inhibitory effect of the HSP65 DNA vaccine from Bacille Calmette Guerrin in the hematogenous metastasis of B16/F10 melanoma,two eukaryotic expression DNA vectors carrying the HSP65 encode gene were pCR3.1-VS-HSP65 and pCR3.1-VS-HSP65-TP-M2.Male C57BL/6J mice were continuously immunized intramuscularly 8 times in 8 weeks using above two DNA vaccines.The specific Anti-HSP65 antibody was detected by ELISA method.Two weeks after last immunization,B16/F10 melanomas cells were intravenously inoculated to investigate the immunogenicity and pharmacodynamic action of these vaccines.The results showed that the specific anti-HSP65 antibodies were detected in the antiserum of the male C57BL/6J mice immunized with the above two HSP65 DNA vaccines.pCR3.1-VS-HSP65-TP-M2 could significantly induce the higher antibody titer than pCR3.1-VS-HSP65 and significantly inhibit the hematogenous metastasis of B16/F10 melanoma.Tumor inhibitory rate was 74.8%(liver)and 53.2%(lung)compared with saline control group.HSP65 DNA vaccine can significantly suppress the hematogenous metastasis of B16/F10 melanoma on the basis of enhancing immunogenicity.
【Key words】 Heat shock protein; HSP65; DNA vaccine; Melanoma; Tumor inhibitory rate;
- 【文献出处】 药物生物技术 ,Pharmaceutical Biotechnology , 编辑部邮箱 ,2009年02期
- 【分类号】R739.5
- 【被引频次】4
- 【下载频次】179