Ds-02 * Induction of Autophagy Markers in Gliomas Following Pharmacological Notch Blockade
Year: 2014
Type: conference-abstract
Abstract: BACKGROUND: Induction of autophagy has been identified as a potential mechanism for chemotherapeutic resistance, and its manipulation has increasingly been explored as a treatment strategy in many cancers. However, there is minimal data on the effects of the Notch pathway on autophagy in cancer, and none in gliomas. We therefore examined if Notch pathway blockade using a gamma-secretase inhibitor (GSI) would induce autophagy in glioma neurosphere lines. METHODS: 500,000 cells from 3 neurosphere lines (HSR-GBM1, 040622, and 040821), maintained in Neurocult medium supplemented with EGF and FGF, were treated for 48 hours with DMSO, 2 µM or 5 µM levels of GSI. Protein was extracted from cell lysates and Western blotting was performed using primary antibodies specific for LC3B, pAkt, Akt, pERK, and ERK, as well as β-actin. RESULTS: A LC3B-II band, suggesting induction of autophagy, was observed after Notch pathway blockade at the higher (5 µM) GSI level in all three cell lines. Inhibition of pAkt was also seen at this dose, but a significant up-regulation of pERK was not observed. CONCLUSIONS: Induction of autophagy, possibly through inhibition of the Akt / mTor pathway, was seen after Notch inhibition in glioma neurospheres using a GSI. These results suggest a possible resistance mechanism to Notch inhibition in malignant gliomas.
Source: Neuro-Oncology
Institution: Johns Hopkins University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2332729724