Investigation for pancreatic cancer associated with hypoxia-inducible factor

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Wakayama Medical University
• Principal Investigator: TANI Masaji Wakayama Medical University, Second Department of Surgery, Associate Professor, 医学部, 講師 (60236677)
• Co-Investigator(Kenkyū-buntansha): YAMAUE Hiroki Wakayama Medical University, Second Department of Surgery, Professor, 医学部, 教授 (20191190) ; IWAHASHI Makoto Wakayama Medical University, Second Department of Surgery, Associate Professor, 医学部, 講師 (70244738) ; UCHIYAMA Kazuhisa Wakayama Medical University, Second Department of Surgery, Assistant Professor, 医学部, 助教授 (80232867)
• Project Period (FY): 2004 – 2006
• Keywords: pancreatic cancer / chemosensitivity / Gemcitabine / HIF

Research Abstract

Surgery is the most effective treatment for pancreatic cancer patients. However, almost pancreatic cancer patients have been diagnosed as unresectable disease by distant metastasis, and resectable pancreatic cancer patients have a high incidence of recurrence of pancreatic cancer. Therefore, it is necessary to develop the effective chemotherapy for chemoresistant pancreatic cancer. Pancreatic cancer is hypo-vascular tumor suggesting hypoxia by computed tomography with a contrast medium. It was thought that microenvironment of pancreas makes cancer cells induce chemoresistance of pancreatic cancer cells having chemosensitivity in vitro.
We demonstrated the IC50 against pancreatic cancer cells line, MiaPaCa2 and PANC1 by Gemcitabine (GEM), CDDP and 5-FU. The IC50 of MiapaCa2 for GEM under hypoxia was 72.1±12.1 ng/ml compared with 30.5±1.5 ng/ml under normoxia (P=0.03), and that of PANC1 under hypoxia was 5884.4±4590.0 ng/ml compared with 890.3±78.0 ng/m under normoxia (P=0.0006). There was no significant difference between hypoxia and normoxia in chemosensitivities for CDDP and 5-FU. In addition, we conducted that the investigation of gene expression using microarray. Although hypoxia-inducible factor was not detected by microarray, the genes of hypoxia -inducible protein 2, CXCR4, angiopoietin-like 4, endothelin2, placental growth factor and cascular endothelial growth factor-related protein which were involved in hypoxia and angiogenesis expressed strongly by hypoxia.
It was concluded that these genes have potential for the new drugs for pancreatic cancer.