Sorafenib inhibits neuroblastoma cell proliferation and signaling, blocks angiogenesis, and impairs tumor growth

Nisha C. Kakodkar, Radhika R. Peddinti, Yufeng Tian, Lisa J. Guerrero, Alexandre Chlenski, Qiwei Yang, Helen R. Salwen, Michael L. Maitland, Susan L. Cohn

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Background: More effective therapy for children with high-risk neuroblastoma is desperately needed. Preclinical studies have shown that neuroblastoma tumor growth can be inhibited by agents that block angiogenesis. We hypothesized that drugs which target both neuroblastoma cells and tumor angiogenesis would have potent anti-tumor activity. In this study we tested the effects of sorafenib, a multi-kinase inhibitor, on neuroblastoma cell proliferation and signaling, and in mice with subcutaneous human neuroblastoma xenografts or orthotopic adrenal tumors. Procedure: Mice with subcutaneous neuroblastoma xenografts or orthotopic adrenal tumors were treated with sorafenib, and tumor growth rates were measured. Blood vessel architecture and vascular density were evaluated histologically in treated and control neuroblastoma tumors. The in vitro effects of sorafenib on neuroblastoma proliferation, cell cycle, and signaling were also evaluated. Results: Sorafenib inhibited tumor growth in mice with subcutaneous and orthotopic adrenal tumors. Decreased numbers of cycling neuroblastoma cells and tumor blood vessels were seen in treated versus control tumors, and the blood vessels in the treated tumors had more normal architecture. Sorafenib treatment also decreased neuroblastoma cell proliferation, attenuated ERK signaling, and enhanced G 1/G 0 cell cycle arrest in vitro. Conclusions: Our results demonstrate that sorafenib inhibits the growth of neuroblastoma tumors by targeting both neuroblastoma cells and tumor blood vessels. Single agent sorafenib should be evaluated in future phase II neuroblastoma studies. Pediatr Blood Cancer 2012;59:642-647.

Original languageEnglish (US)
Pages (from-to)642-647
Number of pages6
JournalPediatric Blood and Cancer
Volume59
Issue number4
DOIs
StatePublished - Oct 2012

Keywords

  • Angiogenesis
  • Extracellular signal-regulated MAP kinases
  • Neuroblastoma
  • Sorafenib

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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