The study for chemoresistance of ovarian cancer to notice c-Jun signaling pathway

• Project/Area Number: 15K20125
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Yamagata University
• Principal Investigator: SEINO Manabu 山形大学, 医学部, 助教 (40594320)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 卵巣がん / 化学療法抵抗性 / がん幹細胞 / JNK阻害薬 / c-Jun / JNK

Outline of Final Research Achievements

Chemoresistance of ovarian cancer poses a major obstacle to the successful management of this devastating disease. We found that specific JNK inhibitor, SP600125, treatment sensitizes cytotoxic drugs such as paclitaxel and cisplatin. This result suggests that JNK and its signal transduction might have a key role in the resistance of ovarian cancer cells to chemotherapy.
Additionally, we examined whether AS602801, a newly developed JNK inhibitor as the therapeutic agent for inflammatory endometriosis and which is revealed the safety in the Phase 2 clinical study, has the anti-cancer effects and inhibiting cancer stem cells in vitro and in vivo. AS602801 has modest cytotoxic activity on cancer stem cells in vitro and clearly inhibits tumor-initiating capacity in vivo. These findings suggest that AS602801 is a promising anti-cancer stem cell agent.

Research Products

• [Journal Article] The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. (2016)
  • Author(s): Okada M, Kuramoto K, Takeda H, Watarai H, Sakaki H, Seino S, Seino M, Suzuki S, Kitanaka C.
  • Journal Title: Oncotarget Volume: 19 Issue: 19 Pages: 27021-27032
  • DOI: 10.18632/oncotarget.8395
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Time-staggered inhibition of JNK effectively sensitizes chemoresistant ovarian cancer cells to cisplatin and paclitaxel (2016)
  • Author(s): Seino M, Okada M, Sakaki H, Takeda H, Watarai H, Suzuki S, Seino S, Kuramoto K, Ohta T, Nagase S, Kurachi H, Kitanaka C
  • Journal Title: Oncology Reports Volume: 35 Issue: 1 Pages: 593-601
  • DOI: 10.3892/or.2015.4377
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] GSKJ4, A Selective Jumonji H3K27 Demethylase Inhhibitor, Effectively Targets Ovarian Cancer Stem Cells (2015)
  • Author(s): Sakaki H, Okada M, Kuramoto K, Takeda H, Watarai H, Suzuki S, Seino S, Seino M, Ohta T, Nagase S, Kurachi H, Kitanaka C
  • Journal Title: Anticancer Res. Volume: 35 Pages: 6607-6614
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Requirement of JNK Signaling for Self-renewal and Tumor-initiating Capacity of Ovarian Cancer Stem Cells (2015)
  • Author(s): Seino M, Okada M, Shibuya K, Seino S, Suzuki S, Takeda H, Ohta T, Kurachi H, Ito K, Nagase S, Kitanaka C
  • Organizer: American Association for Cancer Research Annual Meeting
  • Place of Presentation: アメリカ（フィラデルフィア）
  • Year and Date: 2015-04-21