抗βhCG蛋白疫苗的抗肿瘤作用  

Anti-Tumor Effects of Protein Vaccine against Human Chorionic Gonadotrophin Beta(βhCG)

作　　者：叶嘉燕[1] 胡向兵[1] 邢芸[1] 侯景[1] 李飞[1] 张帆[1] 金亮[1] 李泰明[1] 刘景晶[1] 曹荣月[1] 

机构地区：[1]中国药科大学生命科学与技术学院微基因药物实验室,江苏南京210009

出　　处：《药物生物技术》2010年第5期386-392,共7页Pharmaceutical Biotechnology

基　　金：国家自然科学基金(30772570;30872393);中央高校基本科研业务费专项资金资助(JKY2009021;JKQ2009022)

摘　　要：以人绒毛膜促性腺激素β亚基（βhCG）的羧基端109~118的6段串联重复表位为靶点、热休克蛋白65（HSP65）为载体,设计一种新型的蛋白疫苗HSP65-X6-βhCGCTP37,探讨其能否抑制小鼠前列腺癌,并且对其抗肿瘤的作用机理进行部分探讨。以制备的HSP65-X6-βhCGCTP37免疫C57BL/6小鼠,分别检测体液免疫应答和细胞免疫应答。通过ELISA法,从血清中检测到高滴度的抗βhCGIgG类抗体。Western blot实验证明小鼠血清中的抗体能够特异性识别βhCG表位。淋巴细胞增殖实验的结果显示,HSP65-X6-βhCGCTP37的免疫能够有效的刺激脾淋巴细胞的增殖。预防性实验的结果显示,HSP65-X6-βhCGCTP37激发的免疫应答对于RM-1肿瘤攻击起到有效的保护作用,与PBS阴性对照组比较,平均肿瘤重显著降低（P〈0.05）。同时有效地减少了小鼠的肺转移（P〈0.01）;抑制了小鼠皮内肿瘤模型中的血管新生（P〈0.01）。HSP65-X6-βhCGCTP37蛋白疫苗能有效地抑制小鼠前列腺癌的生长。To explore whether 6 tandem repeats of antigen epitopes β-hCG（109~118）fused with HSP65 can effectively inhibit RM-1 prostate cancer in tumor-bearing mice and to study the mechanism of β-hCG on anti-tumor,the C57 BL/6 mice were immunized with HSP65-X6-βhCGCTP37.After the last immunization,humoral immune and cellular immune responses were detected.High titer of anti-β-hCG antibody was detected in immunized mice sera by ELISA and verified by Western blot analyses.Splenic lymphocyte proliferation assay results showed that the proliferation activity of splenocytes from mice immunized with HSP65-X6-βhCGCTP37 fusion protein was significantly high.The results of prophylactic experiment showed that HSP65-X6-βhCGCTP37 immunization significantly inhibited the growth of RM-1 tumor in mice.The average tumor weight was in the mice immunized with HSP65-X6-βhCGCTP37,significantly lower than that of mice injected with PBS（P0.05）.HSP65-X6-βhCGCTP37 significantly reduced the number of pulmonary metastases in mice（P0.01）.Meanwhile,it also attenuated tumor-induced angiogenesis in intradermal tumor model in mice（P0.01）.HSP65-X6-βhCGCTP37 can effectively suppress the growth of prostate cancer in mice.

关 键 词：人绒毛膜促性腺激素β亚基 HSP65-X6-βhCGCTP37 蛋白疫苗 前列腺癌 

分 类 号：R965[医药卫生—药理学]