目的探索肝细胞肝癌治疗的新策略。方法构建抗血管生成基因kallistatin真核表达载体。建立小鼠皮下H22肝癌动物模型,分别采用kallistatin基因治疗,美洛昔康治疗以及联合治疗,测量肿瘤体积,Western blot检测肿瘤内kallistatin基因及凋亡相关蛋白的表达,免疫组织化学方法检测肿瘤细胞的增殖、肿瘤内微血管密度。结果与空质粒对照组相比,kallistatin基因及美洛昔康治疗均能使肿瘤体积缩小(P〈0.05),联合治疗更显著抑制了肿瘤的生长(P〈0.01),抑制肿瘤细胞增殖,减少肿瘤内微血管密度,增加bax的表达。结论美洛昔康联合抗血管生成治疗能有效抑制小鼠肝癌的生长,为肝癌的治疗提供了新的方向。
Objective To explore new strategy to treat liver cancer.Methods A eukaryotic expression vector encoding kallistatin was constructed.Subcutaneous H22 tumors were established in BALB/c mice and were treated by kallistatin-pcDNA3.1(+),meloxicam and meloxicam + kallistatin-pcDNA3.1(+),empty pcDNA3.1(+) served as control.The volumes of tumors were measured,expression of kallistatin and apoptosis-associated proteins were detected by Western blot,proliferation of tumor cells and microvessel density(MVD) were examined through immunohistochemistry stain.Results Compared with the control group,either kallistatin or meloxicam monotherapy reduced the size of tumors(P〈 0.05),and a significant reduction of tumor volume was found in the combining therapy group(P 〈0.01).The results showed inhibition of cell proliferation,reduction of MVD and upregulation of the expression of bax in the combining therapy group.Conclusion Combination of meloxicam and anti-angio-genic therapy can inhibit the growth of liver cancer implanted in mice effectively and provides a new strategy for liver cancer treatment.