Inhibition of autophagy potentiates the efficacy of Gli inhibitor GANT-61 in MYCN-amplified neuroblastoma cells.

ABSTRACT:

Background

Aberrant Hedgehog (Hh) signaling is often associated with neuroblastoma (NB), a childhood malignancy with varying clinical outcomes due to different molecular characteristics. Inhibition of Hh signaling with small molecule inhibitors, particularly with GANT-61, significantly suppresses NB growth. However, NB with MYCN amplification is less sensitive to GANT-61 than those without MYCN amplification.

Methods

Autophagic process was examined in two MYCN amplified and two MYCN non-amplified NB cells treated with GANT-61. Subsequently, chemical and genetic approaches were applied with GANT-61 together to evaluate the role of autophagy in GANT-61 induced cell death.

Results

Here we show that GANT-61 enhanced autophagy in MYCN amplified NB cells. Both an autophagic

SUBMITTER: Wang J 

PROVIDER: S-EPMC4210511 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature