Role of gap junctional intercellular communication on the cytotoxic effect of anticancer drug

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591377
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kurume University
• Principal Investigator: TANAKA Toshiaki Kurume University, Department of Surgery, instructor, 医学部, 助手 (20227151)
• Co-Investigator(Kenkyū-buntansha): TANAKA Yuichi Kurume University, Department of Surgery, instructor, 医学部, 助手 (50268900) ; YAMANA Hideaki Kurume University, Department of Surgery, Professor, 医学部, 教授 (30140669) ; NAGANO Takeshi Kurume University, Department of Surgery, instructor, 医学部, 助手 (00389305)
• Project Period (FY): 2004 – 2005
• Keywords: esophageal cancer / chemotherapy / gap junction

Research Abstract

We investigate the role of gap junctional intercellular communication(GJIC)on the cytotoxic effect of an anticancer drug, docetaxel, in esophageal cancer cell line.
RT-PCR and Western blot analysis revealed that human esophageal cancer cell line, KE-10, didn't have expression of any connexin (Cx) and GJIC capacity. Cx32 gene was transfected into the cells. Cx32 expression was confirmed with RT-PCR, Western blot and immunohistochemisty in the Cx32-transfected cells (KE-10/Cx32). KE-10/Cx32 showed the restoration of GJIC capacity with dye transfer assay and the cyotoxicity was enhanced by 30-40% compared with KE-10. Apoptosis was upregulated in KE-10/C32 cells. And MDR gene, which is responsible for the drug resistance of docetaxel, wasn't expressed in two cell lines. Finally, we investigated the effect of the GJIC inhibitor, carbenoxolone, on cytotoxic effect of docetaxel. Carbenoxolone decreased the cytotoxity of docetaxel in KE-10/Cx32 cells by 20%. These date suggest that GJIC is involved in the cytotoxic effect of docetaxel.