Experimental Study Of The Effects Of Endostatin On The Model Of Neck Lymph Node Metastasis Of Human Tongue Squamous Cell Carcinoma In Nude Mice

Object:To observe the effect of endostatin on the growth, vascular generation and metastasis of tongue squamous carcinoma in mice. And analyze the possible mechanisms of endostatin which inhibited vascular generation.Method:In this study, we establish orthotopic implantation model of human tongue carcinoma in nude mice by Tca83cells. The mice were randomly divided into groups A, B and C. Group A was given subcutaneous injections of saline solution0.1ml; group B and group C were given endostatin10mg/kg/d and20mg/kg/d, respectively. Drugs were administered daily for two weeks. We observe the characteristic of tumor growth and lymph node metastases in our model. And use immunohistochemical method to mark the vasculars in the tumor and detect the expression of VEGF-C. And then we count vascular density and VEGF-C positive rate. Data were analysis by SPSS20.0software package.Result:1. Tumor in the experimental group grows slowly compared to the control group. Tumor size was5.838±0.095mm3,3.554±0.061mm3and2.578±0.074mm3respectively in group A, B and C at the end of experiment, which shows endostatin could inhibit tumor growth. Further, we calculate microvascular density in each specimen. Group A was10.4±1.26. Group B was4.4±0.84and group C was2.2±0.79, which suggests endostatin could inhibit tumor angiogenesis, and the ability of inhibition was more powerful with the increase of the dose.2. The mice of high dose group has a lower lymphatic metastasis rate than those of the control group and the low dose group. Group A was50%; group B was20%; group C was0%, which shows high dose endostatin could inhibit tumor lymphatic metastasis. Further, we calculate microvascular density in each specimen. Group A was6.2±0.92; Group B was4.0±1.05; Group C was2.2±0.92, which suggests endostatin could inhibit tumor lymphangiogenesis, and the ability of inhibition was more powerful with the increase of the dose.3. In addition, VEGF-C positive rate was80%in group A,40%in group B, and20%in group C. High doses endostatin could decrease the expression of VEGF-C in the tumor cells.Conclusion:1. Tumor angiogenesis play an important role in tumor growth. Endostatin could inhibit tumor angiogenesis, thus inhibit tumor growth and the ability was dose dependent, but we did not see its effect of reduction or elimination of the tumor.2. Tumor lymphangiogenesis play an important role in the process of invasion and metastasis of malignant tumor, high doses endostatin could inhibit tumor lymphangiogenesis, thus inhibit tumor lymphatic metastasis.3. Endostatin may inhibit tumor lymphangiogenesis by decreasing the expression of VEGF-C.