减毒沙门菌介导联合基因对腺样囊性癌血管生成的抑制作用

Attenuated Salmonella-mediated fusion genes inhibit tumor angiogenesis in BALB/c mice with human salivary adenoid cystic carcinoma

目的:观察构建含有Tip30与人IFN-γ基因的真核表达及共表达质粒的重组减毒沙门菌对腺样囊性癌荷瘤裸鼠肿瘤血管生成的抑制作用。方法:4周龄BALB/cnunu雄鼠25只,随机分成5组,对照组(PBS组)、单纯减毒沙门菌组(SL7207组)、携带人IFN-γ基因减毒沙门菌治疗组(SL7207/pCIIFN组)、携带Tip30基因减毒沙门菌治疗组(SL7207/pCITip30组)、携带Tip30与人IFNγ基因的真核共表达质粒的重组减毒沙门菌治疗组(SL7207/pCITip30/IFN组),均于颌下接种腺样囊性癌(ACC2)细胞。10d后对照组裸鼠口服PBS,其余各治疗组口服相应的减毒沙门菌,隔周1次,共3次。然后检测肿瘤生长体积、带瘤存活期、裸鼠体内肿瘤的微血管密度(MVD)。结果:各治疗组比较对照组、携带基因治疗组比较SL7207组、联合基因治疗组比较单基因治疗组肿瘤生长慢、体积小,带瘤存活期长(P<0.05);携带Tip30基因治疗组MVD较其他3组低,联合基因组较携带Tip30单基因组MVD低(P<0.05)。结论:减毒沙门菌载体分别介导Tip30、IFN-γ基因有抑制肿瘤生长作用,联合基因较单基因治疗效果好,有协同作用。

Objective:To observe the inhibitory effect of recombinant attenuated Salmonella typhimurium(AST) harboring eukaryotic expression plasmids encoding (Tip30, IFN-g and Tip30 fused with human IFN-g gene) on tumor angiogenesis in BALB/c mice with human salivary adenoid cystic carcinoma. Methods: Twenty-five 4-week-old BALB/c male nude mice were equally randomized into 5 groups: control group (PBS group), simple attenuated Salmonella group (SL7207 group), AST harboring plasmid pCI-IFN group (SL7207/pCI-IFN group), AST harboring plasmid pCI-Tip30 group(SL7207/pCI-Tip30 group), and AST harboring co-expressing plasmid pCI-Tip30/IFN group (SL7207/pCI-Tip30/IFN group). BALB/c mice in all groups received submandibular administration of ACC-2 cells suspension. The control group received oral PBS 10 d after injection, and the other groups received different recombinant Salmonella typhimuria 3 times weekly. Then the tumor size, tumor-bearing survival time and tumor microvascular density (MVD) in ACC-2 tumor were determined. Results: Compared with the control group, the tumor sizes of the 4 treatment groups were smaller and the tumor-bearing survival times were longer (P< 0.05). Compared with the SL7207 group, tumor sizes of Tip30 and human IFN-g gene treatment groups were smaller and the tumor-bearing survival times were longer (P<0.05). Compared with the single gene groups, the tumor size of the fusion genes treatment group were smaller and the tumor-bearing survival time were longer (P<0.05). Compared with the other 3 groups, the microvascular of density the 2 treatment groups harboring Tip30 gene was lower. Compared with the treatment group harboring Tip30 gene, the microvascular density of the fusion gene treatment group was lower (P<0.05). Conclusion: Both AST-mediated Tip30 gene treatment and IFN-g gene treatment can inhibit tumor growth, and the fusion gene treatment of the 2 has better inhibitory effect than the single gene, indicating that there is synergy between the 2 genes.