Yano Motoki, Nakashima Yoshiaki, Kobayashi Yoshihiro, Mizuno Kotaro, Konishi Akimitsu, Sasaki Hidefumi, Fukai Ichiro, Scheule Ronald K, Fujii Yoshitaka
Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan.
Cancer Gene Ther. 2004 May;11(5):354-62. doi: 10.1038/sj.cgt.7700704.
Intravenous endostatin gene transfection results in tumor suppression in a murine pulmonary metastasis model. We transfected the endostatin gene at different times, in order to achieve an optimal protective effect. pST2-Endo encoding murine endostatin was injected in a complex with cationic lipid. Pulmonary metastases were caused by intravenous injection of murine fibrosarcoma cells. Mice were observed for 14 days following fibrosarcoma cell inoculation (FSI). In the study groups, the animals were transfected with pST2-Endo at three different times: 2 days before and 3 and 7 days after FSI. In the group transfected with pST2-Endo 2 days before FSI, the weights of the lungs and tumor-occupied area ratio were significantly less than in the other groups. Significant inhibition of tumor neovascularization was documented by means of CD31 immunohistochemistry. The effect of repeated endostatin transfection on survival after FSI was determined. Animals repeatedly transfected with the endostatin gene survived significantly longer than the groups treated with a single endostatin gene transfection. A stable endostatin-expressing fibrosarcoma transfectant was created and tested for migration and invasion. Compared with controls, endostatin expression reduced migration and invasion by 15%. It is concluded that endostation gene transfection before FSI and repeated transfection thereafter results in significant tumor suppression.
静脉内内皮抑素基因转染在小鼠肺转移模型中可导致肿瘤抑制。我们在不同时间转染内皮抑素基因，以实现最佳的保护效果。将编码小鼠内皮抑素的pST2-Endo与阳离子脂质复合后注射。通过静脉注射小鼠纤维肉瘤细胞诱导肺转移。在接种纤维肉瘤细胞（FSI）后观察小鼠14天。在研究组中，动物在三个不同时间用pST2-Endo转染：FSI前2天以及FSI后3天和7天。在FSI前2天用pST2-Endo转染的组中，肺重量和肿瘤占位面积比显著低于其他组。通过CD31免疫组织化学证实肿瘤新生血管形成受到显著抑制。确定了内皮抑素重复转染对FSI后生存的影响。用内皮抑素基因重复转染的动物比单次内皮抑素基因转染治疗的组存活时间显著更长。构建了稳定表达内皮抑素的纤维肉瘤转染细胞，并对其迁移和侵袭进行了检测。与对照相比，内皮抑素表达使迁移和侵袭减少了15%。结论是，FSI前进行内皮抑素基因转染并在此后重复转染可导致显著的肿瘤抑制。
