抗βhCG多表位融合蛋白疫苗治疗实验小鼠黑色素瘤的机制研究  

Mechanism Study on the Anti-melanoma Effects of Vaccines against Ectopic Human Chorionic Gonadotrophin Beta(eβhCG)

作　　者：杨洁[1,2] 柳祖辉 程乾[1] 李曼曼 袁玉婷 苗梓韬 李慧忠[1] 金亮 曹荣月 

机构地区：[1]徐州医学院江苏省肿瘤生物治疗重点实验室,江苏徐州221002 [2]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》2015年第6期471-475,共5页Pharmaceutical Biotechnology

基　　金：国家级大学生创新创业训练计划项目(No.J1030830);国家自然科学基金(No.331270985;No.81172973;No.81373232和No.81202015);江苏省高校自然科学基金面上项目(No.12KJB320014;No.13KJB320028);miR-26a靶向TET酶在胰腺成体干细胞分化过程中的作用及机制研究(No.20140029)

摘　　要：以融合蛋白HSP65-X10-βh CGCTP37作为免疫原,免疫荷瘤小鼠和未荷瘤小鼠,观察其对小鼠黑色素瘤B16-F10的体内治疗作用,以及其对肿瘤在体内的血管增生及肺转移的影响,并对其体内抗肿瘤的作用机理进行初步探讨。结果显示,HSP65-X10-βh CGCTP37的治疗对于小鼠黑色素瘤的攻击起到了有效的保护作用,与PBS对照组比较,实验组小鼠的平均瘤重显著降低(P<0.05);有效抑制了肿瘤细胞的血管增生和肺转移;免疫后小鼠的血清中产生了特异性的高滴度抗体。说明HSP65-X10-βh CGCTP37蛋白疫苗能够激发小鼠的有效免疫应答、抑制黑色素瘤的血管增生和转移,从而抑制肿瘤的生长。The β-subunit of human chorionic gonadotropin( β-h CG) is ectopically expressed in various types of cancer. It has been utilized as an antigenic target in anti-cancer vaccines. In the therapeutic anti-tumor immunity experiment,C57 BL /6J male mice were immunized with HSP65-X10-βh CGCTP37 fused protein by subcutaneous injection for 3 times,after being loaded subcutaneously by B16-F10 cells. And the mice were sacrificed 2 weeks after tumor implantation. In the other experiment,mice were vaccined with HSP65-X10-βh CGCTP37 by subcutaneous injection for 4 times at biweekly intervals,and sera were collected weekly for immunoassay after the initial immunization. On the 14 th day after the last immunization,B16-F10 cells were loaded intracutaneously into mice for angiogenesis study,and tail intravenous injected for pulmonary metastasis study. Compared with PBS group,the average weight of tumors of the vaccined mice was much lower. Meanwhile,it also attenuated tumor-induced angiogenesis in intradermal tumor model and pulmonary metastasis in tail-vein tumor model. Besides,humoral immune response was effectively elicited. In summary,it has been verified that the administration of HSP65-X10-βh CGCTP37 could effectively inhibit growth,angiogenesisi,and metastasis of B16-F10 melanoma in vivo.

关 键 词：人绒毛膜促性腺激素 热休克蛋白65 蛋白疫苗 黑色素瘤 肺转移 血管增生 体液免疫 

分 类 号：R739.5[医药卫生—肿瘤]