Study of the local immune system monitoring and anti-tumor immune escape mechanism in cervical cancer development

• Project/Area Number: 16K20173
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: EGUCHI SATOKO 東京大学, 医学部附属病院, 助教 (80707810)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: survivin / cervical cancder / TRAIL / HPV / resveratrol / cervical caner / エピゲノム解析 / ヒトパピローマウイルス / 子宮頸部異形成 / 子宮頸がん / 子宮頸部局所免疫 / エピゲノム

Outline of Final Research Achievements

Loss of p53 function due to HPV infection induces resistance to apoptosis in cervical cancer cells. TRAIL, which induces apoptosis in a p53-independent manner, may provide an alternative strategy for treating cervical cancer. Survivin, an antiapoptotic protein that is highly expressed in cancer cells, regulates apoptosis and the cell cycle. We investigated the therapeutic potential of targeting survivin, while focusing on the TRAIL-induced apoptosis pathway. The viability and cell cycle of HPV16-positive CaSki and SiHa cells were assessed after survivin knockdown by small interfering RNA (si-survivin). The small molecule YM155 and resveratrol were used as survivin inhibitors. Targeting of survivin expression might be an ideal strategy for cervical cancer treatment as it would decrease viable cell number and enhance apoptosis sensitivity. Further, combination therapy with TRAIL, rather than cisplatin, may be compatible with the proposed survivin-targeting strategy.

Research Products

• [Journal Article] Therapeutic significance of targeting survivin in cervical cancer and possibility of combination therapy with TRAIL (2018)
  • Author(s): Nakamura H, Taguchi A, Kawana K, Baba S, Kawata A, Yoshida M, Fujimoto A, Ogishima J, Sato M, Inoue T, Nishida H, Furuya H, Yamashita A, Eguchi S, Tomio K, Mori-Uchino M, Adachi K, Arimoto T, Wada-Hiraike O, Oda K, Nagamatsu T, Osuga Y, Fujii T
  • Journal Title: Oncotarget Volume: 9 Issue: 17 Pages: 13451
  • DOI: 10.18632/oncotarget.24413
  • Peer Reviewed / Open Access
• [Journal Article] Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): A new approach to finding targets for cervical cancer stem cell treatment. (2017)
  • Author(s): Ogishima J
  • Journal Title: oncotargeｔ Volume: 印刷中
  • Peer Reviewed
• [Journal Article] STAT3 activity regulates sensitivity to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in cervical cancer cells. (2016)
  • Author(s): Nakamura H
  • Journal Title: Int J Oncoｌ Volume: 49 Pages: 2155-2162
  • Peer Reviewed