Analysis of anticancer drug-resistant ovarian cancer cells under hypoxic tumor microenvironment

• Project/Area Number: 21890130
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: HAYASHI Masami Osaka University, 医学系研究科, 助教 (00551748)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2010: ¥1,235,000 (Direct Cost: ¥950,000、Indirect Cost: ¥285,000); Fiscal Year 2009: ¥1,365,000 (Direct Cost: ¥1,050,000、Indirect Cost: ¥315,000)
• Keywords: 卵巣癌 / 抗癌剤耐性 / Akt / mTOR

Research Abstract

Paclitaxel-resistant ovarian cancer cells showed the activation of Akt and significantly higher levels of Akt2 expression compared with paclitaxel-sensitive cells. An HIF-2α expression was also higher in paclitaxel-resistant cells than in paclitaxel-sensitive cells.
We next examined the significance of Akt2 in paclitaxel-resistant in vivo tumor growth by selectively inhibiting Akt2. An siRNA targeting Akt2 inhibited ovarian tumor growth in nude mice. These results indicated molecular target treatment against either Akt2 or HIF-2α would be useful for the paclitaxel-resistant ovarian cancer.

Research Products

• [Journal Article] Requirement of evading apoptosis for HIF-1α-induced malignant progression in mouse cells. (2011)
  • Author(s): Hayashi M, Yoo YG, Christensen J, Huang LE.
  • Journal Title: Cell Cycle. in press
• [Journal Article] Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary. (2010)
  • Author(s): Mabuchi S, Kawase C, Altomare DA, Morishige K, Hayashi M, Sawada K, Ito K, Terai Y, Nishio Y, Klein-Szanto AJ, Burger RA, Ohmichi M, Testa JR, Kimura T.
  • Journal Title: Mol Cancer Ther 9 Pages: 2411-2422
• [Journal Article] An essential role of the HIF-1alpha-c-Myc axis in malignant progression. (2009)
  • Author(s): Yoo YG, Hayashi M, Christensen J, Huang LE.
  • Journal Title: Ann N Y Acad Sci. 1177 Pages: 198-204
• [Journal Article] mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary. (2009)
  • Author(s): Mabuchi S, Kawase C, Altomare DA, Morishige K, Sawada K, Hayashi M, Tsujimoto M, Yamoto M, Klein-Szanto AJ, Schilder RJ, Ohmichi M, Testa JR, Kimura T.
  • Journal Title: Clin Cancer Res. 15 Pages: 5404-5413
• [Journal Article] mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary. (2009)
  • Author(s): Mabuchi S, Kawase C, Altomare DA, Morishige K, Sawada K, Hayashi M, et al.
  • Journal Title: Clin Cancer Res. 15 Pages: 5404-5413
  • Peer Reviewed