Down-regulation of MDR1 by Ad-DKK3 via Akt/NFκB pathways augments the anti-tumor effect of temozolomide in glioblastoma cells and a murine xenograft model

Journal of Neuro-oncology
Toshitaka FujiharaYasushi Takagi

Abstract

Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1. GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination. Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway. Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.

References

Dec 1, 1991·Journal of Neurosurgery·M W NaborsO M Colvin
Sep 1, 1989·Molecular and Cellular Biology·J E ChinI B Roninson
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Mar 11, 2005·The New England Journal of Medicine·Monika E HegiRoger Stupp
Jun 27, 2007·Virchows Archiv : an International Journal of Pathology·Silvia FattoriMaura Castagna
Apr 30, 2008·Neuro-oncology·Yoshifumi MizobuchiShinji Nagahiro
Jul 18, 2009·Molecular Cancer Research : MCR·Guido Frosina
Jun 19, 2013·Cellular and Molecular Life Sciences : CMLS·Chiara RigantiDavide Schiffer
Jul 24, 2014·Molecular Cancer Therapeutics·Jessian L MunozPranela Rameshwar

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