重组人血管内皮抑素联合化疗治疗乳腺癌的实验研究

Recombinant Human Endostatin Combined with Vinorelbine-cisplatin Chemotherapy in Treatment of Human Breast Cancer Xenograft in Nude Mice

关键词:  乳腺癌  重组人内皮抑素  化疗  血管内皮生长因子  HIF-1α  P53

Key words:  breast cancer  recombinant human endostatin  chemotherapy  VEGF  HIF-1α  P53

摘要:

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。

Abstract:

OBJECTIVE To investigate the anti-angiogenesis and tumor inhibitory effects of recombinant human endostatin(rhES) combined with vinorelbine-cisplatin chemotherapy(NP regimen) on xenograft tumors in nude mice of human breast carcinoma cell MDA-MB-435S. METHODS Forty xenograft nude mice were randomized into 4 groups: NP group (vinorelbine and cisplatin), rhES group (rhES), rhES+NP group(combined treatment as above-mentioned), and control group (normal saline). Inhibitory rate of xenograft and tumor growth curve was calculated and plotted. MVD, VEGF, HIF-1α and P53 were measured by immunohistochemistry. RESULTS Tumor inhibition rate of the rhES+NP group was 64.63%, but that of the NP group was 35.47%. Compared with the other 3 groups, MVD of the rhES+NP group significantly reduced, the difference was statistically significant (P<0.05). HIF-1α, VEGF and P53 of the rhES+NP group was significantly lower than of the control group and the NP group, the difference was statistically significant(P<0.05). CONCLUSION Experiments show that rhES combined with NP regimen can effectively control the tumor growth and decrease tumor MVD in nude mice, which may down-regulated the expression of VEGF and HIF-1α. The mechanism of rhES on P53 needs further study.