Development of the new treatment in oral cancer related to mitochondrial apoptosis

• Project/Area Number: 24792209
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Kobe University
• Principal Investigator: HASEGAWA TAKUMI 神戸大学, 医学(系)研究科(研究院), 助教 (50546497)
• Research Collaborator: TAKEDA Daisuke ; UEHA Takeshi ; KAWAMOTO Teruya ; KOMORI Takahide
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 炭酸ガス / 低酸素 / 扁平上皮癌 / 口腔癌 / 転移

Outline of Final Research Achievements

In this study, we examined the effects of transcutaneous CO2 on cancer apoptosis and lymphogenous metastasis using human SCC xenografts. Our results showed that transcutaneous CO2 affects expressions of PGC-1α and TFAM and protein levels of cleavage products of caspase-3, caspase-9 and PARP, which relatives mitochondrial apoptosis. They also showed that transcutaneous CO2 significantly inhibits SCC tumor growth and affects expressions of HIF-1α, VEGF, MMP-2 and MMP-9, which play essential roles in tumor angiogenesis, invasion and metastasis. In conclusion, transcutaneous CO2 suppressed tumor growth, increased mitochondrial apoptosis and decreased the number of lymph node metastasis in human SCC by decreasing intra-tumoral hypoxia and suppressing metastatic potential with no observable effect in vivo. Our findings indicate that transcutaneous CO2 could be a novel therapeutic tool for treating human SCC.

Research Products

• [Journal Article] Transcutaneous Carbon Dioxide Induces Mitochondrial Apoptosis and Suppresses Metastasis of Oral Squamous Cell Carcinoma In Vivo． (2014)
  • Author(s): Takeda D, Hasegawa T, Ueha T, Imai Y, Sakakibara A, Minoda M, Kawamoto T, Minamikawa T, Shibuya Y, Akisue T, Sakai Y, Kurosaka M, Komori T．
  • Journal Title: PLOS ONE Volume: 9 Issue: 7 Pages: e100530-e100530
  • DOI: 10.1371/journal.pone.0100530
  • NAID: 120005611288
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ミトコンドリア経路に関連した口腔癌新規治療法の開発 (2014)
  • Author(s): 武田大介、長谷川巧実、今井佑輔、榊原晶子、明石昌也、南川 勉、渋谷恭之、古森孝英
  • Organizer: 第59回日本口腔外科学会総会・学術大会
  • Place of Presentation: 千葉
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] ミトコンドリア経路に関連した口腔癌新規治療法の開発 (2013)
  • Author(s): 武田大介、長谷川巧実、今井佑輔、榊原晶子、重田崇至、南川 勉、渋谷恭之、古森孝英．
  • Organizer: 題58回日本口腔外科学会総会
  • Place of Presentation: 福岡