Nrf2 영구 넉다운 난소암 세포주의 Proteasome 저해 항암제 Bortezomib에 대한 감수성 증가

• 영문명: Enhanced Sensitivity to Proteasome Inhibitor Bortezomib in Nrf2 Knockdown Ovarian Cancer Cells
• 발행기관: 대한약학회
• 저자명: 이상황(Sanghwan Lee) 최보현(Bo-Hyun Choi) 곽미경(Mi-Kyoung Kwak)
• 간행물 정보: 『약학회지』제55권 제6호 (2011년), 466~472쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2011.12.31

영문 초록

NF-E2-related factor 2 (Nrf2), a master regulator of antioxidant genes in animals, has been associated with the resistance of cancer cells to several cytotoxic chemotherapeutics. Bortezomib, a reversible inhibitor of the 26S proteasome, is a novel class anti-cancer therapeutics approved for the treatment of refractory multiple myeloma. However, the molecular mechanism of drug-resistance remains elusive. In the present study, bortezomib sensitivity has been investigated in Nrf2 knockdown ovarian cancer cells. When Nrf2 expression is stably repressed using interfering RNA expression, bortezomibinduced apoptosis and cell death were significantly enhanced compared to nonspecific RNA control cells. Knockdown cells showed elevated expression in the catalytic subunit PSMB5, PSMB6, and PSMB7 compared to the control, and failed to induce heme oxygenase-1 expression following bortezomib treatment. These indicate that differential proteasome levels and altered expression of stress-response genes could be underlying mechanisms of bortezomib sensitization in Nrf2-inhibited ovarian cancer cells.

키워드

Bortezomib 26S proteasome Nrf2 PSMB5 Ovarian cancer