| Literature DB >> 33750814 |
Miguel Angel Merlos Rodrigo1,2, Hana Michalkova1,2, Vladislav Strmiska1,2, Berta Casar3, Piero Crespo3, Vivian de Los Rios4, J Ignacio Casal4, Yazan Haddad1,2, Roman Guran1,2, Tomas Eckschlager5, Petra Pokorna6, Zbynek Heger1,2, Vojtech Adam7,8.
Abstract
Metallothionein-3 has poorly characterized functions in neuroblastoma. Cisplatin-based chemotherapy is a major regimen to treat neuroblastoma, but its clinical efficacy is limited by chemoresistance. We investigated the impact of human metallothionein-3 (hMT3) up-regulation in neuroblastoma cells and the mechanisms underlying the cisplatin-resistance. We confirmed the cisplatin-metallothionein complex formation using mass spectrometry. Overexpression of hMT3 decreased the sensitivity of neuroblastoma UKF-NB-4 cells to cisplatin. We report, for the first time, cisplatin-sensitive human UKF-NB-4 cells remodelled into cisplatin-resistant cells via high and constitutive hMT3 expression in an in vivo model using chick chorioallantoic membrane assay. Comparative proteomic analysis demonstrated that several biological pathways related to apoptosis, transport, proteasome, and cellular stress were involved in cisplatin-resistance in hMT3 overexpressing UKF-NB-4 cells. Overall, our data confirmed that up-regulation of hMT3 positively correlated with increased cisplatin-chemoresistance in neuroblastoma, and a high level of hMT3 could be one of the causes of frequent tumour relapses.Entities:
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Year: 2021 PMID： 33750814 PMCID： PMC7943580 DOI： 10.1038/s41598-021-84185-x
Source DB: PubMed Journal: Sci Rep ISSN： 2045-2322 Impact factor: 4.379