| Breast cancer is the second leading cause of cancer deaths in women today ,after lung cancer, and is the most common cancer among women. From year to year, the incidence and the morbility of breast cancer are increasing. The conservative treatments for breast cancer include radiotherapy, chemotherapy, and endocrine therapy. Recent years, bio-targeted therapy becomes becomes a novel strategy In 1971, Folkman reported the theory of angiopoiesis. If there is no blood vessel neogenesis, tumor growth will be inhibited within 2-3mm in diameter. As solid cancer, the grwoth of breast cancer depends on blood vessel neogenesis, which supplys nutrient. The gene of blood vessel endothelium is stable, and drug resistance seldom occurs . It is known that endostatin is one of the antiangiogenesis, which is formed by 184 amino acids, 22KD of molecular weight. China-made rhES has been commercialized under the trade name"Endostar". Our institute carried out clinical trial (Phase II and III), demonstrating a good effect of Endostar combined with chemotherapy on treating non small cell lung cancer. However, there is a lack of experimental research on ES combined with chemotherapy in treating breast cancer. In this study, MCF-7 breast cancer cell line and nude mice with human breast cancer were treated with recombinant human endostatin. Then we observed the inhibition of tumor proliferation, the apoptosis of cancer cells, and the blood vessel neogenesis of the tumors. The inhibitive effect of rhES combined with Paclitaxel-cisplatin on human breast cancer was evaluated by comparison with Group single chemotherapy, Group single rhES, and Group sodium,respectively.Methods 1. The cultured MCF-7 human breast cancer cells were subcutaneously injected into the breast of each nude mouse in situ.2. 48 nude mice bearing human breast carcinoma were devided into Team A and Team B randomly, then every team were subdivided 4 groups. Group combined-drug were given espectively both rhES and TP: paclitaxel, 20mg/kg, ip, d1, d7, d14; DDP, 5mg/kg, d1, d7; rhES, 10mg/kg, d1-14. Group single chemotherapy, were given paclitaxel, 20mg/kg, ip, d1, d7, d14; DDP, 5mg/kg, d1, d7. Group single rhES were given rhES 10mg/kg. And Group sodium were given equal volume sodium.3. Microvessel density (MVD) in tumors were detected by immunohistochemistry. And apoptosis was tested by TUNEL staining.4. Serum VEGF was determined by ELISA.5. Survial time was observed in Team B.Results1. 10 days after implantation, the mice were all observed tumor appearancing.2. Tumor volume: tumors of Group combined-drug grew more slowly than other groups(P<0.05). Group combined-drug, 343.6057±214.55573; Group single chemotherapy, 809.2204±196.46286; Group single rhES, 1085.8786±157.46491; Group sodium 1227.9323±350.45055.3. The expression of MVD of Group combined-drug is lower than that of other groups (P<0.05). Group combined-drug, 22.1667±5.98052; Group single chemotherapy, 37.3333±6.80196; Group single rhES, 32.0000±3.34664; Group sodium, 48.0000±3.40588.4. Serum VEGF of Group combined-drug is lower than other groups (P<0.05). Group combined-drug, 33.5±2.16795; Group single chemotherapy, 45.6667±3.55903; Group single rhES, 41.3333±4.92612; Group sodium, 73.6667±3.50238.5. Apoptotic index was increased in Group combined-drug(P<0.05).6. There was no significantly difference of survival time between Group combined-drug and Group single chemotherapy (P>0.05). But the survival time of Group combined-drug is siginificantly longer than that of Group sodium (P<0.05). Conclusion rhES combined TP chemotherapy on nude mice bearing human breast cancer can inhibit tumor growth more siginificantly than single TP chemotherapy. The reason may be that rhES can decrease serum VEGF, reduce microvessel growth inhibition, and induce apoptosis of tumors. Our study provides the evidence on endostar combined chemotherapy in clinical treatment of breat cancer.
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