| 谭叶,王效军,李美玲,陆海军.重组人内皮抑素联合放疗对小鼠胃癌移植瘤的生长抑制作用及机制的研究[J].中华放射医学与防护杂志,2017,37(3):187-192 |
| 重组人内皮抑素联合放疗对小鼠胃癌移植瘤的生长抑制作用及机制的研究 |
| The inhibitory effect of endostar combined with radiotheraphy on gastric transplantation tumorinmice |
| 投稿时间：2016-09-17 |
| DOI：10.3760/cma.j.issn.0254-5098.2017.03.005 |
| 中文关键词: 重组人内皮抑素 辐射 微血管密度 G蛋白信号调节因子5 乏氧诱导因子-1α |
| 英文关键词:Recombinant human endostatin Radiotherapy Microvessel density G-protein signaling 5 Hypoxia-induced facter-1α |
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| 中文摘要: |
| 目的 通过重组人内皮抑素（商品名：恩度）联合照射对小鼠胃癌移植瘤生长抑制情况及G蛋白信号调节因子5（regulator of G-protein signaling 5，RGS5）、血管内皮生长因子（vascular endothelia grouth factor，VEGF）和乏氧诱导因子-1α（hypoxia-induced factor HIF-1α）表达的影响，探讨抗血管生成治疗联合照射协同抑瘤作用的可能机制。方法 制备32只胃癌移植瘤小鼠模型，将其按随机数字表法分为生理盐水对照组（NS对照组）、恩度组、单纯照射组（RT组）、恩度联合照射组（恩度+RT组），共4组，每组8只。通过肿瘤生长曲线和抑瘤率两个指标比较4种治疗对小鼠移植瘤的生长抑制作用，应用免疫组织化学法，计算肿瘤组织中微血管密度（MVD）值及检测RGS5、VEGF、HIF-1α的表达情况差异及相关性分析。结果 抑瘤作用RT组、恩度+RT组与NS对照组、恩度组比较差异有统计学意义（t=7.4、5.6，P<0.05），其中，恩度+RT组抑瘤作用最强。恩度组、RT组及恩度+RT组的MVD值均降低，恩度+RT组最明显。恩度组、RT组及恩度+RT组HIF-1α表达比对照组减弱，其中联合组最明显，差异有统计学意义（t=6.5、8.2、13.1，P<0.05）。与对照组相比，RT组VEGF、RGS5表达量升高，恩度组和联合组表达量降低，但恩度+RT组与恩度组表达差异无统计学意义（P>0.05）。Pearson相关分析发现，RGS5、VEGF表达与HIF-1α的表达呈正相关（r=0.57、0.71，P<0.05）。结论 恩度联合照射可通过抑制肿瘤HIF-1α的表达，下调VEGF、RGS5的表达，抑制移植瘤血管生成，使肿瘤血管趋于正常化，改善乏氧抑瘤效果好。 |
| 英文摘要: |
| Objective To observe the effect of endostatin(Endostar)combined with radiotheraphy on the growth, microvessel density (MVD), the expressions of regulators of G-protein signaling 5 (RGS5),vascular endothelial growth factor (VEGF) and hypoxia-induced factor-1α (HIF-1α) ingastric transplantation tumor, and to explore underlying mechanism. Methods Thirty-two tumor-bearing mice were randomly divided into four groups including control group, ES group,RT group and ES+RT group. Then the tumor-bearing mice survival and tumor volume alterations were observed. After treatments of drug and RT, the inhibition rate of tumor growth and tumor MVD were measured.Immunohistochemical staining method was used to detect the expressions of RGS5,VEGF and HIF-1α.Results Compared with the ES group and control group, the ES+RT and RT treatment had effective anti-tumor effect(t=7.4,5.6,P<0.05), where as the ES+RT was more obvious in anti-tumor with the lowest value of MVD in tumor. Compared with the control group, the expression of HIF-1α in ES group, RT group, and especially ES+RT group was significantly reduced(t=6.5,8.2,13.1,P<0.05). The expression levels of VEGF and RGS5 wereincreased in RT group but was reduced in ES group and ES+RT group, and the expressions of VEGF and RGS5 in ES group and ES+RT group had no significant difference(P>0.05). Rank correlation analysis showed the expression of HIF-1α and the expressions of VEGF and RGS5 were positively correlated(r=0.57, 0.71,P<0.05).Conclusions A possible mechanism of Endostar combined with radiotherapy on tumor growth inhibition may due to the inhibition of HIF-1α and its downstream VEGF and RGS5, and then inhibit tumor angiogenesis that results in the recovery of tumor blood vessels and tumor oxygen supplement. |
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