MDR glioblastoma cell lines were created in response to prolonged doxorubicin chemotherapy. [[CD133]], [[DNA dependent protein kinase]] (DNA-PK) and [[MDR protein 1]] (MDR1) were markedly elevated in these cells. 

CD133 and DNA-PK may increase MDR1 via the [[phosphoinositide 3 kinase]] (PI3K)-[[Akt]] [[signaling pathway]]. PI3K downstream targets Akt and [[nuclear factor]] [[NF-κB]], which interacts with the MDR1 promoter, were also elevated in these cells. Downregulation of CD133 and DNA-PK by small interfering RNA, or inhibition of PI3K or Akt, decreased Akt, NF-κB and MDR1 expression. The results indicate that CD133 and DNA-PK regulate MDR1 through the PI3K- or Akt-NF-κB signal pathway. Consequently, a novel chemotherapeutic regimen targeting CD133 and DNA-PK in combination with traditional protocols may increase chemotherapeutic efficacy and improve prognosis for individuals who present with glioblastoma
((Xi G, Hayes E, Lewis R, Ichi S, Mania-Farnell B, Shim K, Takao T, Allender E, 
Mayanil CS, Tomita T. CD133 and DNA-PK regulate MDR1 via the PI3K- or Akt-NF-κB
pathway in multidrug-resistant glioblastoma cells in vitro. Oncogene. 2015 Mar
30. doi: 10.1038/onc.2015.78. [Epub ahead of print] PubMed PMID: 25823028.)).