高强度聚焦超声对人胰腺癌裸鼠移植瘤差异性表达基因的影响

Effect of high- intensity focused ultrasound on the differential expression genes in nude mouse models with transplanted human pancreatic cancer

目的研究高强度聚焦超声(HIFU)辐照人胰腺癌移植瘤后差异性表达基因,从基因组学初步探讨HIFU的生物学机制。方法构建人胰腺癌裸鼠YY-1移植瘤模型,HIFU辐照后采用Agilent人类基因表达谱芯片检测差异性表达基因,反转录-聚合酶链反应(RT-PCR)技术验证上调基因HIF1a、SMAD4及下调基因Bcl-xl。结果与未辐照对照组相比,辐照组表达谱芯片分析发现与胰腺癌相关的差异性基因共65个,其中上调43个,下调22个。基因本体(GO)分析提示显著表达改变的基因富集于细胞核、细胞质部位,并与蛋白结合、金属离子结合、锌离子结合、转录调控、细胞凋亡等功能相关。RT-PCR检测结果与表达谱芯片分析结果一致。结论 HIFU辐照可引起一系列基因调控改变,这些差异性表达基因可能参与调控肿瘤生物学过程。

Objective To investigate the effect of high-intensity focused ultrasound （HIFU） on the differential expression genes in nude mouse models with transplanted human pancreatic cancer, and based on the genomics to make a preliminary discussion on the biological mechanism of HIFU. Methods YY-1 transplanted tumor models of human pancreatic cancer were established in nude mice. After HIFU irradiation, the differential expression genes were identified by using Agilent human gene expression spectrum chip, and reverse transcription polymerase chain reaction （RT-PCR） technique was employed to verify the up-regulated genes HIF1A and SMAD4, as well as the down-regulated gene Bcl-xl. Results Compared with the control group （non-irradiation group）, the analysis of Agilent human gene expression spectrum chip revealed that the differential genes that were related to pancreatic cancer had 65 genes in total, among them 43 genes were upregulated and 22 genes were down-regulated. Gene ontology analysis indicated that the genes that showed significantly altered expression were enriched in the nucleus and cytoplasm, and they were related to some functions, including protein binding, metal ion binding, zinc ion binding, regulation of transcription, apoptosis, etc. The results of RT-PCR detection were consistent with those of Agilent human gene expression spectrum chip analysis. Conclusion HIFU irradiation can cause a series of changes in gene regulation, and these differential expression genes may participate in the regulation of tumor biological process.