Autophagic flux inhibition enhances cytotoxicity of the receptor tyrosine kinase inhibitor ponatinib.

ABSTRACT:

Background

Despite reported advances, acquired resistance to tyrosine kinase inhibitors still represents a serious problem in successful cancer treatment. Among this class of drugs, ponatinib (PON) has been shown to have notable long-term efficacy, although its cytotoxicity might be hampered by autophagy. In this study, we examined the likelihood of PON resistance evolution in neuroblastoma and assessed the extent to which autophagy might provide survival advantages to tumor cells.

Methods

The effects of PON in inducing autophagy were determined both in vitro, using SK-N-BE(2), SH-SY5Y, and IMR-32 human neuroblastoma cell lines, and in vivo, using zebrafish and mouse models. Single and combined treatments with chloroquine (CQ)-a blocking agent of lysosomal metabolism and aut

SUBMITTER: Corallo D 

PROVIDER: S-EPMC7507635 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature