Down-regulation of MYCN protein by CX-5461 leads to neuroblastoma tumor growth suppression.

ABSTRACT: PURPOSE:MYCN oncogene amplification is an independent predictor of poor prognosis in neuroblastoma. CX-5461 is a small molecular inhibitor that prevents initiation of ribosomal RNA (rRNA) synthesis by RNA Pol I, down-regulating MYCN/MYC proteins. We hypothesize that neuroblastoma tumor growth can be suppressed by CX-5461. METHODS:MYCN-amplified (KELLY, IMR5) and nonamplified (SY5Y, SKNAS) neuroblastoma cells were treated with CX-5461. MYCN/MYC expression after 24-48 h was determined by Western blot. Orthotopic neuroblastoma tumors created in mice using KELLY cells were treated with CX-5461-loaded silk films implanted locally. Tumor growth was monitored using ultrasound. Histologic evaluation of tumors was performed. RESULTS:IC50 for KELLY, IMR5, SY5Y, and SKNAS cells to CX-5461 was 0.75 μM

SUBMITTER: Taylor JS 

PROVIDER: S-EPMC6545249 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature