The Experimental Research for Analysis and Treatment of Invasion of Ora Cancer. (Inhibitory effects regarding MMP production as target.)

2000 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671987
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: OKAYAMA UNIVERSITY
• Principal Investigator: NISHIYAMA Akiyoshi Okayama University, Dental School, Instructor, 歯学部, 助手 (50189320)
• Co-Investigator(Kenkyū-buntansha): SASAKI Akira Okayama University, Dental School, Associate Professor, 歯学部, 助教授 (00170663)
• Project Period (FY): 1999 – 2000
• Keywords: MMP / Invasion / MMP Inhibitor / Orthotopic implantation

Research Abstract

Invasion and metastasis are the most important and complex factors determining cancer treatment. Many studies have shown that some matrix metalloproteinases (MMPs) play essential roles in tumor metastasis and invasion. Recently, some MMP inhibitors have been developed and would be expected to limit the tumor growth and formation of metastasis. MMI-166, is a newly developed MMPs inhibitor that can be administered orally and has a more potent and selective inhibitory activit of MMP-2 and MMP-9, both related to tumor invasion and metastasis. We examined the effect of MMP inhibitor, MMI-166, in an experimental tongue cancer model in nude mice using human oral cancer cells.
Experimental tongue cancer model was obtained by the injection of human oral cancer cell line, HSC-3 producing MMP-2 and MMP-9, into the tongue of nude mice. From the same day, MMI-166 (1.8 mg/mouse/day) was orally administered once a day for 12 days. The control group received normal saline solution instead of MMI-166. The tumor size was evaluated by the method described by Kikuchi et al. and the mode of invasion was determined by histological evaluation.
The MMI-166 treated animals presented tumors 60% smaller than the MMI-166-untreated group. Histological examination of the tongue of the untreated group revealed that tumor aggressively invaded into the surrounding muscle and blood vessels. On the other hand, MMI-166 inhibited the invasion of cancer cells and no infiltrating cells were observed in the tumor margins. MMI-166 did not inhibit the growth of HSC-3 cancer cells in vitro. These results suggested that the inhibitory activity of MMI-166 for the tumor growth at tongue should be due to the inhibition of matrix metalloproteinases but the direct anticancer activity.
The anti-cancer drug without cytotoxic effects MMI-166 is potentially effective for the treatment of human oral cancer.