z-logo
open-access-imgOpen Access
EZH2 inhibition decreases neuroblastoma proliferation and in vivo tumor growth
Author(s) -
Laura V. Bownes,
Arthur Robin Williams,
Raoud Marayati,
Laura L. Stafman,
Hooper R. Markert,
Colin H. Quinn,
Nikita Wadhwani,
Jamie M. Aye,
Jerry E. Stewart,
Karina J. Yoon,
Elizabeth MroczekMusulman,
Elizabeth A. Beierle
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0246244
Subject(s) - neuroblastoma , gene knockdown , cancer research , viability assay , cell growth , biology , carcinogenesis , ezh2 , cell culture , motility , in vivo , tumor progression , cancer , microbiology and biotechnology , epigenetics , biochemistry , genetics , gene
Investigation of the mechanisms responsible for aggressive neuroblastoma and its poor prognosis is critical to identify novel therapeutic targets and improve survival. Enhancer of Zeste Homolog 2 (EZH2) is known to play a key role in supporting the malignant phenotype in several cancer types and knockdown of EZH2 has been shown to decrease tumorigenesis in neuroblastoma cells. We hypothesized that the EZH2 inhibitor, GSK343, would affect cell proliferation and viability in human neuroblastoma. We utilized four long-term passage neuroblastoma cell lines and two patient-derived xenolines (PDX) to investigate the effects of the EZH2 inhibitor, GSK343, on viability, motility, stemness and in vivo tumor growth. Immunoblotting confirmed target knockdown. Treatment with GSK343 led to significantly decreased neuroblastoma cell viability, migration and invasion, and stemness. GSK343 treatment of mice bearing SK-N-BE(2) neuroblastoma tumors resulted in a significant decrease in tumor growth compared to vehicle-treated animals. GSK343 decreased viability, and motility in long-term passage neuroblastoma cell lines and decreased stemness in neuroblastoma PDX cells. These data demonstrate that further investigation into the mechanisms responsible for the anti-tumor effects seen with EZH2 inhibitors in neuroblastoma cells is warranted.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here