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Phosphatidylinositol 3-kinase and TIMP-3 genes were found to be related to the progression of colon cancer during laparoscopic surgery in a murine model.

在小鼠模型中，发现磷脂酰肌醇 3-激酶和 TIMP-3 基因与腹腔镜手术期间结肠癌的进展有关。

基本信息

批准号：
15591411
负责人：
UTSUNOMIYA Tohru
金额：
$ 2.11万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Objective : The aim of this study was to determine the gene expression patterns of laparoscopic procedures to identify any benefits in comparison with laparotomy procedures.Summary and background data : Laparosopic surgery has been performed on a wide variety of patients because of the clinical benefits of perioperative recovery, result in a better survival than an open colectomy. However, no basic and molecular-biological examinations have yet to elucidate the mechanisms of such an increased survival.Methods : To examine the gene expression profiles of mice innoculated with colon cancer cells, the tumors, the livers and the lungs of mice were analyzed using a microarray after either laparoscopic treatment, an open laparotomy or anesthesia alone.Results : In the laparotomy and control group, we observed a significant enhancement of tumor growth in comparison to the laparoscopic group. When analyzing the genes became more remarkably upregulated or downregulated in the laparoscopic group in comparison to those in the laparotomy or control group, we focused our attention on the TIMP-3 gene and PI3-kinase gene expression. The downregulation of TIMP-3,which played an important role in enhancing invasion the activity of the tumor cells, and the upregulation of PI3-kinase were observed. To confirm the downstream signal of the PI3-kinase gene, we examined the expression of Skp-2 gene and p27 protein, which were key molecules for regulating the cell cycle. We observed that the expression level of the Skp-2 to be upregulated, while the expression level of p27 protein decreased.Conclusion : These results suggest that the surgical procedures of a laparotomy induced a dwonregulation of TIMP-3 and an upregulation of PI3-kinase, which together resulted in an enhancement of cancer cell growth leading to an increased invasion activity and cell cycle in comparison to treatment using a laparoscopic approach.

目的：本研究的目的是确定腹腔镜手术与开腹手术相比的基因表达模式，以确定与开腹手术相比有何益处。摘要和背景数据：由于围手术期恢复的临床好处，腹腔镜术已在各种患者中进行，导致比开腹结肠切除术有更好的生存。然而，目前还没有基本的和分子生物学的研究来阐明这种提高存活率的机制。方法：利用基因芯片技术分析了腹腔镜组、开腹手术组和单纯麻醉组小鼠肿瘤、肝脏和肺组织的基因表达谱。结果：开腹手术组和对照组的肿瘤生长明显高于腹腔镜组。当腹腔镜组与开腹组或对照组相比，基因表达明显上调或下调时，我们将注意力集中在TIMP-3基因和PI3-激酶基因的表达上。TIMP-3表达下调，PI3-Kinase表达上调，TIMP-3在肿瘤细胞侵袭中起重要作用。为了确认PI3-K基因的下游信号，我们检测了调节细胞周期的关键分子Skp-2基因和p27蛋白的表达。我们观察到Skp-2的表达水平上调，而p27蛋白的表达水平下降。结论：这些结果表明，开腹手术导致TIMP-3的表达上调和PI3-Kinase的上调，共同导致癌细胞生长加速，导致细胞侵袭活性和细胞周期的增加。