恩度不同给药时相联合放疗对胃癌裸鼠移植瘤抑制及其机制研究

Endostar Given at Different Times Combined with Radiotherapy to the Effect of Gastric Cancer Transplanted in Mice and Its Possible Mechanism

摘要: 目的：观察恩度不同给药时相联合放疗对胃癌裸鼠移植瘤的抑制作用，并对其可能机制进行探讨。方法：建立MFC小鼠胃癌移植瘤模型，随机分成5组：对照组、RT1 + NS组、RT1 + ES组、RT7 + ES组、RT14 + ES组，分别于放疗期间采用生理盐水及恩度干预。于治疗的第8、15天各处死5只小鼠，取出肿瘤，观察并测量各组肿瘤体积变化，绘制肿瘤生长曲线，计算抑瘤率，采用免疫组化方法检测各组肿瘤组织中VEGF、HIF-1α及PCNA的表达情况。结果：RT1 + ES组及RT7 + ES组较其他组肿瘤生长慢、抑瘤率高，差异有统计学意义(P < 0.05)；实验第8天和第15天，VEGF与PCNA蛋白的表达在恩度联合放疗组均有不同程度下降，尤以RT1 + ES组及RT7 + ES组PCNA表达下降最明显，差异有统计学意义(P < 0.05)。结论：恩度联合放疗可能通过调节VEGF、HIF-1α及PCNA的表达等机制，对胃癌裸小鼠发挥肿瘤抑制作用。在恩度第7天行放疗或第1天同步放疗，对胃癌裸鼠移植瘤抑制作用最强。

Abstract: Objective: The aim of this study was to observe the inhibitory effect of endostar given at different times combined with radiotherapy on gastric cancer xenografts in nude mice, and to explore its possible mechanism. Methods: MFC mouse gastric cancer xenograft models were established and randomly divided into 5 groups: control group, RT1 + NS group, RT1 + ES group, RT7 + ES group, RT14 + ES group. Physiological saline and Endo intervention during radiotherapy, on the 8th and 15th day of treatment, 5 mice were sacrificed, tumors were taken out, tumor volume changes were observed and measured, tumor growth curves were drawn, tumor inhibition rate was calculated. VEGF, HIF-1α and PCNA were observed by Immunohistochemistry. Results: The tumor growth of RT1 + ES group and RT7 + ES group was slower and the tumor inhibition rate was higher (P < 0.05). On the 8th and 15th day of experiment, VEGF and the expression of PCNA protein decreased in different degrees in the combination of radiotherapy and Endostar, especially in the RT1 + ES group and the RT7 + ES group. The difference was statistically significant (P < 0.05). Conclusion: During the micro-vascular normalization window induced by Endostar, or Endostar and radiotherapy given at the same time, it is possible to exert tumor suppressive effects on nude mice with gastric cancer by regulating the mechanisms of VEGF, HIF-1α and PCNA expression.