Perhexiline maleate enhances antitumor efficacy of cisplatin in neuroblastoma by inducing over-expression of NDM29 ncRNA

• DOI: 10.1038/srep18144
• Publication Date: 2015-12-17T11:52:54Z
• Authors: Serena Vella; Ilaria Penna; Luca Longo; Giulia Pioggia; Patrizia Garbati; Tullio Florio; Fabio Rossi; Aldo Pagano
• Keywords: 0301 basic medicine; RNA, Untranslated; Cell Survival; Reverse Transcriptase Polymerase Chain Reaction; Perhexiline; Apoptosis; Drug Synergism; Mice, SCID; Survival Analysis; Xenograft Model Antitumor Assays; Article; Tumor Burden; 3. Good health; Gene Expression Regulation, Neoplastic; Neuroblastoma; 03 medical and health sciences; Mice, Inbred NOD; ATP-Binding Cassette Transporters; Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Line, Tumor; Cell Survival; Cisplatin; Drug Synergism; Gene Expression Regulation, Neoplastic; Humans; Mice, Inbred NOD; Mice, SCID; Neuroblastoma; Perhexiline; RNA, Untranslated; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis; Tumor Burden; Xenograft Model Antitumor Assays; Multidisciplinary; Cell Line, Tumor; Antineoplastic Combined Chemotherapy Protocols; Animals; Humans; ATP-Binding Cassette Transporters; Cisplatin

High Risk Neuroblastoma (HR-NB) is a pediatric cancer characterized by high malignancy and remarkable cell heterogeneity within the tumour nodules. In recent study, we demonstrated that in vitro vivo over-expression of non-coding RNA NDM29 (neuroblastoma differentiation marker 29) induces NB differentiation, dramatically reducing their malignancy. Among gene expression changes, differentiated phenotype induced decrease ABC transporters responsible for anticancer drug resistance. Thus, pharmacological induction NDM29, principle, might represent possible novel strategy to increase cytotoxic responses. this work, identify small molecule able induce cells, conferring malignant cells increased susceptibility cisplatin effects. We demonstrate enhances antitumoral effects chemotherapy specifically on initiating/cancer stem sub-population, usually refractory therapies relapse. summary, suggest therapeutical approach possibly useful treat very aggressive cases with poor prognosis. This aims promote "stem-like" render them more susceptible killing action drugs.