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目的研究重组人血管内皮抑素联合化疗方案对人乳腺癌裸鼠移植瘤模型的治疗效应,并进一步探讨其抑制肿瘤血管生成的作用机制。方法将乳腺癌荷瘤裸鼠40只随机分为4组,分别为化疗组、内皮抑素组、联合用药组及对照组。化疗组给予长春瑞滨和顺铂;内皮抑素组给予重组人血管内皮抑素;联合用药组给予长春瑞滨,顺铂,和重组人血管内皮抑素;对照组给予等量的生理盐水。给药期间测量肿瘤大小,实验结束取肿瘤称重,计算肿瘤体积,绘制肿瘤生长曲线并比较各组的抑瘤率。免疫组化方法检测各组肿瘤组织微血管密度(MVD),VEGF,HIF-1α及P53的表达。结果联合用药组抑瘤率为64.63%,化疗组抑瘤率为35.47%。联合用药组与其他3组MVD计数比较明显减少,差异有统计学意义(P<0.05)。与对照组及化疗组相比,联合用药组的VEGF、HIF-1α和P53的表达均明显减少,其差异具有统计学意义(P<0.05)。结论重组人血管内皮抑素联合化疗能够有效控制裸鼠乳腺肿瘤生长,降低肿瘤MVD,其机制可能为下调VEGF及HIF-1α的表达。内皮抑素对P53的作用机制有待于更进一步的研究。
Objective To study the therapeutic effect of recombinant human endostatin combined with chemotherapy on the human breast cancer xenograft model in nude mice and to further explore its mechanism of inhibiting tumor angiogenesis. Methods Forty nude mice bearing breast cancer were randomly divided into 4 groups: chemotherapy group, endostatin group, combination group and control group. The chemotherapy group received vinorelbine and cisplatin, the endostatin group received recombinant human endostatin, and the combination group received vinorelbine, cisplatin and recombinant human endostatin. The control group received the same amount of normal saline. The size of the tumor was measured during the administration, the tumor was weighed at the end of the experiment, the volume of the tumor was calculated, the growth curve of the tumor was drawn, and the tumor inhibition rate of each group was compared. Immunohistochemistry was used to detect the expression of microvessel density (MVD), VEGF, HIF-1α and P53 in each group. Results The combined treatment group had a tumor inhibition rate of 64.63% and the tumor inhibition rate of the chemotherapy group was 35.47%. Compared with the other three groups, the MVD count in the combination group was significantly decreased, the difference was statistically significant (P <0.05). Compared with the control group and the chemotherapy group, the expressions of VEGF, HIF-1α and P53 in the combination group were significantly decreased, the difference was statistically significant (P <0.05). Conclusions Recombinant human endostatin combined with chemotherapy can effectively inhibit the growth of breast cancer in nude mice and reduce the MVD. The possible mechanism is that the expression of VEGF and HIF-1α may be down-regulated. The mechanism of endostatin on P53 remains to be further studied.