Javier de la Rosa1, Javier Asensio-Salazar1, Mehdi H Shahi2, Bárbara Meléndez3, Juan A Rey4, Miguel A Idoate5 and Javier S Castresana1*
1Department of Biochemistry and Genetics, University of Navarra School of Sciences, Pamplona, Spain
2Interdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh, India
3Molecular Pathology Research Unit, Virgen de la Salud Hospital, Toledo, Spain
4diPaz Research Unit, La Paz University Hospital, Madrid, Spain
5Department of Pathology, University of Navarra Clinic, Pamplona, Spain
*Corresponding Author: Javier S Castresana, Department of Biochemistry and Genetics, University of Navarra School of Sciences, Irunlarrea 1, Pamplona, Spain.
Received: June 07, 2017; Published: August 17, 2017
Citation: Javier S Castresana., et al. “Genetic and Functional Characterization of Cyclopamine Resistant Neuroblastoma Cells”. Acta Scientific Cancer Biology 1.1 (2018).
We present a study on neuroblastoma cells, treated with up to six cycles of cyclopamine, an SMO inhibitor of the sonic hedgehog pathway. Several genes involved in apoptosis, cancer stem cell phenotype, and sonic hedgehog pathway regulation were tested for expression before and after treatments. Also, cell proliferation and colony formation in 2D and 3D assay systems were used. The genes related to cancer stem cell phenotypes (CD133 and CD15) seemed to increase their expression after exposition to several treatment cycles, coincident with the idea of neuroblastoma resistance to cyclopamine. MYCN, SMO and BCL-2 equally showed higher expression levels after several cycles of treatment. Cyclopamine treatment of neuroblastoma cells reduced cell proliferation and in vitro tumorigenesis determined by 3D colony formation assays in soft agar. The treatments also induced apoptosis and increased MYCN expression.
As a whole, we may consider cyclopamine a good inhibitor against neuroblastoma along the first stages of the treatment, while resistance to this compound can occur later on. More studies on cyclopamine resistance are needed to better approach to neuroblastoma treatment.
Keywords: Cyclopamine; Neuroblastoma; Sonic Hedgehog; CD133; CD15
Copyright: © 2018 Javier S Castresana., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.