TIMP-3 and Phosphatidylinositol 3-kinase genes were found to be related to the progression of colon cancer in a comparison of pneumoperitoneum and laparotomy in a murine model

Purpose. Laparoscopic surgery has been performed on a wide variety of patients because the clinical benefits of a perioperative recovery result in a better short-time outcome than an open colectomy. However, no basic and molecular-biological examinations have yet to elucidate the mechanisms of such an improved outcome. Method. To examine the gene expression profiles of mice inoculated with colon cancer cells, the tumors, the livers and the lungs of mice were analyzed using a microarray. 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 that 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 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. We observed the expression level of the Skp-2 to be upregulated, while the expression level of p27 protein decreased. Conclusions. The surgical procedures of a laparotomy induced a downregulation of TIMP-3 and an upregulation of PI3-kinase, which together resulted in an enhancement of cancer cell growth thus leading to an increased invasion activity and cell cycle in comparison to treatment using a laparoscopic approach.