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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제24권 제3호
- 발행연도
- 2020.1
- 수록면
- 267 - 276 (10page)
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In the present study, we investigated the effect of oncogenic H-Ras on rat mdr1b expression in NIH3T3 cells. The constitutive expression of H-RasV12 was found to downregulate the mdr1b promoter activity and mdr1b mRNA expression. The doxorubicin-induced mdr1b promoter activity of the H-RasV12 expressing NIH3T3 cells was markedly lower than that of control NIH3T3 cells. Additionally, there is a positive correlation between the level of H-RasV12 expression and a sensitivity to doxorubicin toxicity. To examine the detailed mechanism of H-RasV12-mediated down-regulation of mdr1b expression, antioxidant N-acetylcysteine (NAC) and NADPH oxidase inhibitor diphenylene iodonium (DPI) were used. Pretreating cells with either NAC or DPI significantly enhanced the oncogenic H-Ras-mediated down-regulation of mdr1b expression and markedly prevented doxorubicin-induced cell death. Moreover, NAC and DPI treatment led to a decrease in ERK activity, and the ERK inhibitors PD98059 or U0126 enhanced the mdr1b-Luc activity of H-RasV12-NIH3T3 and reduced doxorubicin-induced apoptosis. These data suggest that RasV12 expression could downregulate mdr1b expression through intracellular reactive oxygen species (ROS) production, and ERK activation induced by ROS, is at least in part, contributed to the downregulation of mdr1b expression.
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참고문헌 (57)
참고문헌 신청
Nakai E / 2009 / Enhanced MDR1 expression and chemoresistance of cancer stem cells derived from glioblastoma / Cancer Invest 27:901~908
Gottesman MM / 2002 / Multidrug resistance in cancer : role of ATP-dependent transporters / Nat Rev Cancer 2:48~58
Silva R / 2015 / Modulation of P-glycoprotein efflux pump : induction and activation as a therapeutic strategy / Pharmacol Ther 149:1~123
Malumbres M / 2003 / RAS oncogenes : the first 30 years / Nat Rev Cancer 3:459~465
Prior IA / 2012 / A comprehensive survey of Ras mutations in cancer / Cancer Res 72:2457~2467
Gottesman MM / 2002 / Multidrug resistance in cancer : role of ATP-dependent transporters / Nat Rev Cancer 2:48~58
Silva R / 2015 / Modulation of P-glycoprotein efflux pump : induction and activation as a therapeutic strategy / Pharmacol Ther 149:1~123
Malumbres M / 2003 / RAS oncogenes : the first 30 years / Nat Rev Cancer 3:459~465
Prior IA / 2012 / A comprehensive survey of Ras mutations in cancer / Cancer Res 72:2457~2467
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