血管生成抑制素和IL-7联合治疗的肿瘤抑制效应

ANTI-TUMOR EFFECT OF GENE THERAPY WITH INTRA-TUMOR INJECTION OF PLASMID DNA ENCODING ANGIOSTAN AND IL-7

目的 探讨采用裸质粒DNA肿瘤内直接注射入方法 ,以观察血管生成抑制素 (Angiostatin) ,和IL 7联合治疗肿瘤的可行性 ,及其可能机制。方法 将构建的血管生成抑制素、IL 7基因真核表达质粒 (每次 10 0 μg/只 ) ,分别或联合注射到接种U14肿瘤细胞 5天后的荷瘤鼠体内 ,以后每隔 7天注射一次 ,共三次。观察荷瘤鼠的存活率、肿块生长情况、以及小鼠整体免疫功能 ,并对肿瘤对照组与联合基因治疗组的肿瘤组织进行病理学及细胞凋亡分析。结果 血管生成抑制素、IL 7、以及两者联合治疗均可不同程度地增加荷瘤鼠的存活率、抑制肿瘤生长和转移、调节免疫功能 ,以联合基因治疗组更显著。病理分析表明联合治疗组肿瘤血管形成显著减少 ,基底部有大量的淋巴细胞浸润 ,肿瘤细胞的凋亡率明显升高。结论 直接裸质粒DNA注射血管生成抑制素和IL 7基因可能成为一种方便、有效的肿瘤治疗方法。

Objective To study the anti tumor effect of nude plasmids encoding Angiostatin, and/or IL 7 injected directly into the tumor in vivo,and the possible mechanism. Methods The U14 cancer cells were replanted subcutaneously into the flank of Swiss mice for 5 days, then the recombinated eukaryotic plasmids encoding Angiostatin and /or IL 7 were injected directly into the tumor (100 μg/mouse). Every 7 days the intra tumor injection was repeated for 3 times. Comparative analysis between control and experimental groups on the survival of mice, the growth of tumor, the apoptosis, and the immune function of mice, were studied pathologically. Results The survival rates of mice were extended and the growth and metastasis of tumor were suppressed with intra tumor injection of Angiostatin and/or IL 7, the co injection of Angiostatin and IL 7 obtained the most distinguished result. The pathological observation showed that the tumor angiogenesis was suppressed, a great deal of lymphocyte infiltrated in to the basilar part of tumor, and the apoptosis rate of cancer cell was increased in the group of co injection with both genes. Conclusion Intra tumor injection of the nude plasmid DNA encoding Angiostatin and IL 7 may be a potential method for tumor gene therapy.$$$$