CDK inhibitors reduce cell proliferation and reverse hypoxia-induced metastasis of neuroblastoma tumours in a chick embryo model

Swadi, Rasha R, Sampat, Keerthika, Herrmann, Anne ORCID: 0000-0002-0858-419X, Losty, Paul D ORCID: 0000-0003-0841-5879, See, Violaine ORCID: 0000-0001-6384-8381 and Moss, Diana J (2019) CDK inhibitors reduce cell proliferation and reverse hypoxia-induced metastasis of neuroblastoma tumours in a chick embryo model. Scientific Reports, 9 (1). 9136-.

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Official URL: https://www.nature.com/articles/s41598-019-45571-8

Abstract

Neuroblastoma is a paediatric cancer with a poor prognosis. This is in part due to widespread metastasis at time of presentation, which is refractory to current treatment modalities. New therapeutic agents that can control not only tumour growth but also metastasis are urgently needed. The differentiation therapy, retinoic acid, is currently used in clinic, leading to terminal differentiation of neuroblastoma cells thus reducing tumour growth in the primary tumour as well as at metastatic sites. However, retinoic acid only works in a subset of patients. We investigated the potential of CDK inhibitors, Palbociclib and RO-3306, on neuroblastoma cell differentiation, tumour progression and metastasis by utilising a 3R compliant cost effective preclinical chick embryo model. In both SK-N-AS and BE(2)C cell lines, when engrafted on the chorioallantoic membrane of chick embryos, we observed a reduction of tumour cell proliferation as well as a reduction in hypoxia preconditioning-driven metastasis by 60%. In addition, the expression of a panel of genes with known roles in metastasis, which increased upon hypoxia-preconditioning, was largely reduced by a CDK1 inhibitor. These results provide a promising alternative to currently existing therapies and might aid the development of new treatment protocols for retinoic acid-resistant patients.

Item Type:	Article
Uncontrolled Keywords:	Cell Line, Tumor, Chick Embryo, Animals, Humans, Neuroblastoma, Neoplasm Metastasis, Disease Models, Animal, Cyclin-Dependent Kinases, Protein Kinase Inhibitors, Cell Death, Cell Differentiation, Cell Proliferation, Tumor Hypoxia
Depositing User:	Symplectic Admin
Date Deposited:	08 Jul 2019 09:47
Last Modified:	19 Jan 2023 00:38
DOI:	10.1038/s41598-019-45571-8
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3049115