MUC1基因疫苗抑制EMT6乳癌生长的实验

Suppressing effect of MUC1 gene vaccine on EMT6 breast cancer growth

目的 :观察MUC1基因疫苗对EMT6乳癌生长的特异性抑制作用 .方法 :采用股四头肌肌肉注射法将构建的MUC1基因疫苗pcDNA3 1 MUC1免疫雌性BALB/c小鼠 ,3wk 1次 ,共 3次 .最后一次基因免疫后第 3周 ,接种表达MUC1的EMT6小鼠乳腺癌细胞 .2wk后观察、记录肿瘤的生长情况 .于肿瘤细胞接种后第 4 5日 ,处死全部动物 ,称量肿瘤的质量 .荷瘤小鼠的瘤组织常规HE染色 .结果 :肿瘤细胞接种后 4 5d ,MUC1预防组、质粒pcDNA3 1对照组及生理盐水阴性对照组EMT6肿瘤大小分别为 (2 5 0± 2 4 3) ,(5 96±2 8 2 )及 (6 18± 35 6 )mm3 (P <0 0 1) ;平均瘤质量为 (1 2 3±0 4 1) ,(2 2 8± 0 6 6 )及 2 36± 0 72 )g(P <0 0 1) ;MUC1基因疫苗预防组仅见 4 0 % (4 / 10 )的小鼠有瘤体形成 ,而pcD NA3 1对照组及生理盐水阴性对照组 10 0 % (10 / 10 )可见瘤体形成、肿瘤生长 .结果表明 ,与pcDNA3 1对照组相比 ,MUC1预防组EMT6肿瘤生长受到明显抑制 (P <0 0 1) ;MUC1预防组小鼠免疫保护有显著差异 (P <0 0 5 ) .病理学检查结果显示 ,与 pcDNA3 1对照组相比 ,MUC1DNA疫苗预防组鼠EMT6肿瘤组织大量坏死 .结论 :MUC1基因疫苗显著抑制EMT6乳癌生长 。

AIM: To observe the special anti EMT6 breast cancer growth effects of the MUC1 gene vaccine. METHODS: Female BALB/c mice were immunized intramuscularly with 100 microgram MUC1 cDNA 3 times at 3 weekly intervals. Three weeks after the last immunization, tumor challenge experiments were performed by using MUC1 expressing tumor cell line EMT6. Tumor growth inhibition and body protection were observed 2 wk later. After 45 d of challenge experiments, all mice were killed and tumors weighted. Histological analysis of tumor tissue was carried out with HE staining. RESULTS: After 45 d of challenge experiments, the volumes of EMT6 tumor in MUC1 cDNA, pcDNA3 1(+), and NS group were respectively (250±24 3) , (596±28 2) and (618±35 6) mm 3( P <0 01). The average masses of EMT6 tumors in those three groups were respectively (1 23±0 41), (2 28±0 66) and (2 36±0 72) g( P < 0 01). There was only 40% tumorigenic rate in MUC1 cDNA group, while there was 100% tumorigenic rate in pcDNA3 1(+) and NS groups. It showed that EMT6 tumor growth in mice of MUC1 cDNA group was obviously suppressed ( P <0 01) and there was a significant body protective effect in mice of MUC1 cDNA group ( P <0 05), compared with that in pcDNA3 1(+) control group. Histological analysis showed that the EMT6 tumor tissues markedly necrosed in mice of MUC1 cDNA group compared with that in pcDNA3 1(+) control group. CONCLUSION: MUC1 gene vaccine can significantly suppress the growth of EMT6 breast cancer, which lays a basis for clinical research.