| Malignant solid tumor, which consists of tumor cells and interstitial tissue, is theserious disease that threatens human health. It is characterized by infinite tumor cell proliferation that supported by according blood supply. Therefore, the proliferation of vascular endothelium and angiogenesis play important role in the malignant transition, tumor proliferation and metastasis. Any kind of medicines, either inhibits tumor cell or vascular endothelial cell, have the anti-neoplasm effects, the previous category includes cytotoxic agents and later one includes anti-angiogenesis drugs.Angiostatin is a tumor-derived angiogenesis inhibitor. A large amount of evidence show that AS specifically inhibits endothelial cell proliferation and migration, blocks neovascularization, promotes the primary tumor disappearance in experiment model, and inhibits the formation of metastasis foci. However, to treat tumor using AS alone is time-consuming, and furthermore, the availability of natural AS is limited. The gene therapy of AS still has some potential problems, such as the unstable expression, low transfection efficiency and the potential viral infection, etc. So AS combined with thetraditional tumor treatment means has already become one of the choice in the treatment of entity tumor. Some study about the combination of AS and X-ray demonstrated that there is a obvious synergy between the anti-angiogenesis role of AS and X-ray. This lay the basis for the treatment of entity tumor using "bi-target". Radioactive nuclide internal irradiation therapy is one of the traditional tumor treatment means, and it has obvious advantage in the diagnosis and treatment of tumor. Some studies have shown that radioiodine-labeled AS had the potency to specifically bind to endothelial cells and acted as a novel tumor imaging agent. It is still unclear whether it has any influence to the hyperplasia activation of endothelial cell that AS labeled with 131I and whether it is applicable in the treatment of entity tumor. In the present study, we designed an experiment to investigate the biological activity and the mechanisms inhibiting tumor growth of 131I-AS.Objective: To observe the proliferation inhibition of 131I-AS on endothelial cell of human umbilical vein and investigate the application value of 131I-AS in solid tumor therapy.Methods:1. In vitro, the primary cultured cells, which were treated by 131I-AS in different concentration and PBS, were observed morphologically under light microscopy, and mitotic cells were counted after stained by hematoxylin and eosin. MTT method was used to detect the inhibitory effects of 131I-AS, AS and 131I on HUVEC.2. In vivo, 30 male C57BL/6 mice Lewis lung carcinoma transplanted in their fore limbs were divided into four groups. When tumors mean diameter reached to 10 mm, tumors were treated with 131I 11.1MBq per mouse, AS 12.5mg / kg, 131I-AS (11.lMBq per mouse, 12.5mg / kg) respectively, and similar volume of NS as control. All drugs were given intraperitoneally and injected every other day for 14 days. The volume of tumors was measured during the treatment. After treatmeat, the expression of CD34 and NFkBp65 were measured by immunohistochemistry.Results:1. In vitro study shown:(1) In the presence of 131I-AS, the proliferation inhibition of HUVEC was shown as the lessened cell growth, decreased counting of mitotic cells and increased growth inhibitory rate.(2) The inhibitory rate of 131I-AS in A ,B, C and D to HUVEC was (23.9± 2.8)%,(58.2±3.9)%,(39.1±4.1)% and (78.4±5.4)% respectively. From 2 to 32g/ ml, AS can inhibit the growth of HUVEC, growth inhibitory rate were from (7.4±5.4) % to (17.6±2.7) % in a dose-dependent pattern. The growth inhibition of 131I was not observed until the radioactivity of 131I was 3.70 GBq/L (growth inhibitory rate was 11.51±2.7%, P< 0.01).2. Animal experiment of bearing-tumor model demonstrated:(1) The growth of transplanted Lewis lung carcinoma was inhibited by 73.3±1.7%, 46.6±3.2%, and 21.0±4.8% at groups treated...
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