Antitumor effect of MEK inhibitor in combination with hyaluronic acid synthesis inhibitor in Malignant pleural mesothelioma cell lines

• Project/Area Number: 25462201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Hyogo Medical University
• Principal Investigator: Ayumi Kuroda 兵庫医科大学, 医学部, 助教 (90642570)
• Co-Investigator(Kenkyū-buntansha): 長谷川 誠紀 兵庫医科大学, 医学部, 教授 (10252438) ; 近藤 展行 兵庫医科大学, 医学部, 講師 (50402889) ; 松本 成司 兵庫医科大学, 医学部, 講師 (60412011) ; 多久和 輝尚 兵庫医科大学, 医学部, 助教 (00412049) ; 橋本 昌樹 兵庫医科大学, 医学部, 助教 (40461074)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 中皮腫 / 悪性胸膜中皮腫

Outline of Final Research Achievements

The pleural fluid of patients with malignant pleural mesothelioma demonstrates high levels of hyaluronic acid. Hyaluronic acid also has a CD44 ligand. In this study, we evaluated the anti-tumor effects of hyaluronan synthase (HAS) and mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors. No effects of HAS inhibitors in some cells were observed, while concentration-dependent anti-tumor effects of HAS and MEK inhibitors were observed. Phosphorylation of ERK was inhibited by MEK inhibitors, and there was a concentration-dependent decrease in CD44 expression. Compared to an untreated group, the groups that received HAS or MEK inhibitors as monotherapy were noted to have suppressed enlargement of subcutaneous tumors. We then compared groups receiving monotherapy to a group receiving a combination of both inhibitors, and found that there was significantly suppressed enlargement of subcutaneous tumors.

Research Products

• [Presentation] Antitumor activity of Trametinib, a MEK1/2 inhibitor, in malignant pleural mesothelioma cells in vitro (2014)
  • Author(s): Hiroyuki Cho, Seiji Matsumoto, Ayumi Kuroda, Masaki Hashimoto, Teruhisa Takuwa, Toshi Menju, Makoto Sonobe, Nobuyuki Kondo, Hiroshi Date, Seiki Hasegawa
  • Organizer: American Association for Cancer Research (AACR) Annual Meeting 2014
  • Place of Presentation: San Diego, California, USA