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[目的]探讨携带自杀基因单纯疱疹病毒胸苷激酶(HSV-tk)的重组乳球菌静脉注射后靶向实体肿瘤组织定殖及联合更昔洛韦(GCV)治疗小鼠黑色素瘤的可能性。[方法]荷瘤小鼠静脉注射乳球菌3d或7d后,将小鼠脾肺肝肾器官和肿瘤组织细胞匀浆后涂布于筛选培养基上,以乳酸菌数量的评价静脉发送乳球菌靶向定殖肿瘤细胞的可能性。以携带HSVtk的重组乳酸乳球菌经静脉途径处理荷瘤小鼠后,通过观测小鼠肿瘤体积变化及小鼠存活率评价相关抗肿瘤效果。[结果]静脉注射乳酸乳球菌3d后在小鼠脾肺肝肾和肿瘤组织内均有乳球菌检出,而7d后仅在肿瘤组织中发现有乳酸乳球菌的分布。与对照相比,静脉注射LL-HSV-tk联合GCV处理能显著抑制小鼠体内肿瘤的生长。[结论]静脉发送携带治疗性分子的乳酸乳球菌能靶向实体肿瘤组织定殖并抑制肿瘤的生长。
[Objective] To explore the possibility of targeting solid tumor tissue after intravenous injection of recombinant HSV-tk carrying suicide gene HSV-tk and the treatment of mouse melanoma with ganciclovir (GCV). [Method] After 3 or 7 days of intravenous injection of Lactococcus in tumor-bearing mice, the spleen-lung, liver and kidney organs and tumor tissue of mice were homogenized and plated on the screening medium. The number of lactobacilli Possibility of colonizing tumor cells. The tumor-bearing mice were treated with HSVtk recombinant Lactococcus lactis by intravenous route to evaluate the anti-tumor effect by observing the changes of tumor volume and the survival rate of mice. [Results] Lactococcus lactis was detected in spleen, lung, liver, kidney and tumor tissues of mice after intravenous injection of Lactococcus lactis for 3 days, and the distribution of Lactococcus lactis was only found in the tumor tissues after 7 days. Compared with the control, intravenous injection of LL-HSV-tk in combination with GCV significantly inhibited tumor growth in mice. [Conclusion] The intravenous delivery of therapeutic Lactococcus lactis can target solid tumor colonization and inhibit tumor growth.