Development of new therapeutic strategy focused on inhibition of Warburg effect against oral cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25861948
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Yamaguchi University
• Principal Investigator: HARADA Toyoko 山口大学, 医学部, 特別医学研究員 (20647937)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: メトフォルミン / 5-FU / Warburg効果 / 口腔癌 / アポトーシス

Outline of Final Research Achievements

We evaluated the efficacy of metformin (Met) and 5-FU combined therapy against human oral squamous cell carcinoma (OSCC). MTT assay and TUNEL assay revealed that Met (4 mg/ml) and 5-FU (2.5 μg/ml) combination treatment effectively inhibited cell growth and induced apoptosis in OSCC cell lines compared to either agent alone. Lactate colorimetric assay detected decreased level of lactate in the supernatants of Met and 5-FU treated cells compared to cells treated with Met or 5-FU. Western blot analysis showed down-regulation of HIF-1α and mTOR expression, and up-regulation of AMPKα in cells treated with Met and 5-FU combination treatment. Combination therapy with Met (200 mg/kg, i.p.) and 5-FU (10 mg/kg, i.p.) for 4 weeks effectively reduced tumor growth (77.6%) compared to Met (59.9%) or 5-FU (52%) alone in nude mice. These findings suggest that Met and 5-FU combined therapy could exert strong antitumor effect against OSCC through the inhibition of Warburg effects.

Free Research Field

歯科口腔外科