Elucidation of molecular mechanism of drug resistance acquisition targeting cancer stem cells of gastric cancer and development of novel treatment

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16561
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: NAKASHIMA yuichiro 九州大学, 医学研究院, 助教 (40733564)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: CD44v9 / 癌幹細胞 / 胃癌 / 5-FU / 薬剤感受性 / 活性酸素

Outline of Final Research Achievements

Gastric cancer patients with CD44v9 high expression (57 cases) showed significantly worse prognosis compared to those with low expression patients (147 cases) (overall survival p=0.001, progression free survival p=0.001). CD44v9 high expression group also showed significantly lower histological therapeutic response compared to low expression group (p=0.025). Knockdown of CD44v9 in gastric cancer cell lines with CD44v9 high expression (MKN45 and NUGC4) increased drug sensitivity to 5-FU with decrease of GSH level and increase of ROS level.

Free Research Field

消化管外科学

Academic Significance and Societal Importance of the Research Achievements

CD44v9発現は癌の浸潤・転移に関わるだけでなく、薬剤の組織学的治療効果と有意に相関していた。細胞株の実験において、CD44v9は細胞内のROSを制御することによって、5-FUの薬剤感受性に影響を与えている可能性がある。以上より、胃癌におけるCD44v9発現は化学療法感受性バイオマーカーとなりうる可能性が示唆された。