巴曲酶抑制肿瘤生长和转移的实验研究

[目的]探讨来源于蛇毒的脑梗死治疗药--巴曲酶对肿瘤生长和转移的抑制作用及其相关的作用机制.[方法]选用高转移特性的小鼠B16-BL6黑色素瘤和U14宫颈癌细胞株制作皮下移植瘤以及实验性肺转移和自然转移模型,探讨了40BU/kg巴曲酶的治疗效果.应用酶联免疫吸附反应(ELISA)方法检测血浆纤维蛋白原浓度,利用免疫组化方法检测肿瘤组织中纤维蛋白原的沉积.[结果]巴曲酶(40BU/kg)可显著抑制B16-BL6和U14皮下移植瘤的生长,其抑制率分别为85.7%和77.4%.巴曲酶可有效地抑制U14的实验性肺转移,对照组的肺表面转移结节数的中位数为133个,而 不同的给药方案(肌肉注射巴曲酶)治疗时肺转移结节数减少到24、24.5、26和52个,并且隔日给药或每4天给药一次的治疗方法均有效地抑制了转移灶的生长.在U14自然转移模型中,巴曲酶可有效地抑制肌肉内肿瘤的生长,并且可有效抑制肺转移和淋巴结转移.巴曲酶在降低血浆纤维蛋白原浓度的同时有效抑制地肿瘤组织基质内纤维蛋白原的沉积.实验显示,巴曲酶对小鼠体重、骨髓及一般健康状况无不良影响.[结论]巴曲酶对肿瘤的生长和转移具有明显的抑制作用,并且无骨髓抑制等毒副作用,在肿瘤治疗中将具有广阔的应用前景.

Experimental Study of Batroxobin on Inhibiting Tumor Growth and Metastasis

To investigate the inhibition effect and mechanisms of Batroxobin, a thrombin-like enzyme prepared from snake venom,on tumor growth and metastasis.The models for subcutaneous tumor growth, experimental metastasis and spontaneous metastasis were established by using B16-BL6 melanoma and U14 cervical carcinoma cell lines all with high potential of metastasis.The level of plasma fibrinogen was detected by using enzyme-linked immunosorbant assay (ELISA).The fibrinogen deposition in tumor tissues was determined by immunohistochemical analysis.Batroxobin 40BU/kg significantly inhibited subcutaneous tumor growth of B16-BL6 melanoma and U14 cervical carcinoma,with growth inhibition rates of 85.7%and 77.4%,respectively.In the experimental metastatic model of U14,a significant reduction in the number of pulmonary metastatic lesion was observed in Batroxobin-treated mice when compared with control mice.The number of metastatic lesion in control mice was 133, while the number reduced to 24, 24.5, 26 and 52 after Batroxobin treatment with various regimens.In the spontaneously metastatic model, Batroxobin not only inhibited primary (intramuscular) U14 tumor growth, but also significantly decreased pulmonary micrometastatic lesions and inhibited lymphatic metastasis.Immunohistochemical analysis showed that Batroxobin greatly decreased the deposition of fibrinogen into the extracellular matrix of B16-BL6 tumors.Furthermore,Batroxobin injections were well tolerated; having no harmful effects on body weight and bone marrow or on the general well-being of the animals.[Conclusion]Our data suggest that Batroxobin can inhibit tumor growth and metastasis without bone marrow depression,and will be a promising agent in cancer therapy.