| Objective:Colorcetal cancer is one of the most common malignancies and the development of metastases is the main cause of death. At present there are several treatment options, including surgery, chemotherapy or both combined, but all these treatment has a poor therapeutic effect and thermotherapy has a variety of clinical side effects and drug problems. Therefore, molecular targeted drugs has become the new developed direction to treat cancer. Molecular targeted drugs suramin combination of 5-fluorouracil has been widely used in treatment of metastatic renal cell carcinoma study. This program has gained obvious effect and significant improvement. In the experiment, the cancer cells were implanted subcutaneously in BALB/C mice and suramin+5-FU were applied to treat the transplantation tumor of colorectal cancer to study the mechanism of its suppression and destruction. This study provides experimental evidence for the clinical application of program.Methods:The mice colorectal cancer line CT-26 was implanted subcutaneously in healthy BALB/C mice forelimb skin.60 successful model mice were divided into 4 groups randomly and there were 15 mice in each group. The mice of control group were injected with normal saline intraperitoneally per day; 5-FU group:30mg/kg, intraperitoneal injection daily; suramin group:15mg/kg, intraperitoneally every three days; combined therapy group: 5-FU daily intraperitoneally injection of 30 mg/kg, and suramin intraperitoneally injection of 15mg/kg every three days.The general state of health were observed daily and the tumor volume were measured every 3 days. Feeding for 40 days, tumor volume growth curve were drew,the tumor volume and weighe inhibition rate were calculated and paraffin sections were prepared for H.E. The expression of microvessel density (MVD) in tumor tissue of mice were detected by immunohistochemistry.Results:1.10,100,200,800μg/ml suramin treat colon cancer CT-26 cells for 48 hours, the CT-26 cells relative inhibition rate were 5%,9%,16%,35% and were dependent on drug concentration way.In this program,we can see that the CT-26 colorectal cancer cells significantly were inhibited by suramin and the high concentration of suramin can significantly inhibit the cell activity.2.The tumor size of treatment groups were 6.08±1.95cm~3,3.12±1.01cm~3,1.56±0.59 cm~3,and the inhibition rates were 50.6%,72.3%,83.7%. Compared with control group,there were significant increases in treated groups and the inhibition rate was significantly different (P<0.05).There were a significant difference among treated groups.3. The changes of behavior of miceIn the course of medication, mice of treatment groups moved quickly, have good mental response and took in food and water freely. There was no obvious adverse reaction in treatment groups. With the gradual growth of the nodules of transplanted tumor, the mice of control group had bad mental state,including eating less water,less activity, weight loss, dull fur and unresponsive.4. Changes of pathologic histologyThe control group showed clonal proliferation of tumor cell and rarely necrosis; treatment groups showed more necrosis. Compared with control group, the treatment groups has the larger range of tumor cells. Combined treatment has the largest rang of cell necrosis.5. The MVD countsThe MVD counts of treatment groups were 12.1±0.9,8.5±0.7,5.6±0.6,3.5±0.5. Compared with control group, MVD counts were markedly decreased in each treated group(P<0.01). The treatment groups were significant different (P<0.01).Conclusion:1. The model that mice colorectal cancer line CT-26 was implanted subcutaneously in BALB/C mice, which had the character,such as the better controllability and comparability on operation,the higher successful rate of transplantation,the shorter time of developing into a cancer. In addition, there was no phenomenon of spontaneous regression.2. In vitro, we can see that suramin can inhibit tumor cell growth. Therefore, the anti-tumor mechanism of suramin may be not only by inhibiting angiogenesis to reduce tumor nutrition supply works,but also inhibiting cell growth through a variety of mechanism to suppress tumor growth.3. In this experiment, we can see that suramin can effectively inhibit tumor angiogenesis and block nutrient supply of tumor cells to inhibit the tumor growth by detecting the tumor MVD.4. In the combined treatment group of this experiment,we can see that low dose of suramin can inhibit angiogenesis and reduce the nutrient supply of tumors to reduce tumor size. Suramin and chemotherapeutic have synergistic antitumor effects without toxity.
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