Effect of Transfection with Human Interferon-β Gene Entrapped in Cationic Multilamellar Liposomes in Combination with 5-Fluorouracil on the Growth of Human Esophageal Cancer Cells

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591397
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nagoya University
• Principal Investigator: KODERA Yasuhiro Nagoya University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (10345879)
• Co-Investigator(Kenkyū-buntansha): KOMURA Sadaaki Nagoya University, Institute of Applied Biochemistry, Head of Research Laboratory, 研究部長 (80211233) ; NAKAO Akimasa Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70167542)
• Project Period (FY): 2003 – 2004
• Keywords: Esophageal cancer Cells / Gene therapy / Human interferon-β gene / Cationic multilamellar liposome / Gene transfection / 5-fluorouracil / S-1 / radiation

Research Abstract

Antiproliferative potencies of humanrecombinantinterferon-β(hIFNβ) geneentrappedin cationic multilamellar liposomes (IAB-1) alone and in combination with antineoplastic agentswasevaluated, using a human esophageal cancer xenograft in vivo.
hIFNβ or IAB-1 were injected into the subcutaneous tumor derived from a human esophageal cancer cell line, WSSC, in the dorsal flank of nude mice. Tumors were harvested 24 hours and 48 hours following the injection, and intratumoral concentrationof hIFNβ was quantified by ELISA. hIFNβ was detectable only in mice treated with IAB-1, suggesting that the production of hIFNβ as a result of gene transfection actually took place.
Xenografts were then treated by intratumoral injection of IAB-1 alone and in combination with intraperitoneal 5FU or oral S-1,all at appropriatedoses. Onlyweak antiproliferative effects were observed, even with the combined treatments. Xenografts were then treated by intratumoral IAB-1, radiation (a single boost of 2 Gy on day 1), and a combination of IAB-1 and radiation. Although the treatment with radiation alone had little effect, a combination with radiation and IAB-1 exhibited an astonishing antiproliferative effect and the disease was stabilized for morethan 3 weeks. No adverse reaction in terms of significant body weight loss was observed in any of the treatment groups in comparison with the control mice. Current findings will become valuable information for clinical application of IAB-1 for patients with locally advanced esophageal cancer.