dc.creator | Vaiou M., Pangou E., Liakos P., Sakellaridis N., Vassilopoulos G., Dimas K., Papandreou C. | en |
dc.date.accessioned | 2023-01-31T10:24:20Z | |
dc.date.available | 2023-01-31T10:24:20Z | |
dc.date.issued | 2016 | |
dc.identifier | 10.1007/s00432-016-2216-2 | |
dc.identifier.issn | 01715216 | |
dc.identifier.uri | http://hdl.handle.net/11615/80334 | |
dc.description.abstract | Purpose: Bortezomib (BTZ) is used for the treatment of multiple myeloma (MM). However, a significant proportion of patients may be refractory to the drug. This study aimed to investigate whether the endothelin (ET-1) axis may act as an escape mechanism to treatment with bortezomib in MM cells. Methods: NCI-H929 and RPMI-8226 (human MM cell lines) were cultured with or without ET-1, BTZ, and inhibitors of the endothelin receptors. ET-1 levels were determined by ELISA, while the protein levels of its receptors and of the PI3K and MAPK pathways’ components by western blot. Effects of ET-1 on cell proliferation were studied by MTT and on the ubiquitin proteasome pathway by assessing the chymotryptic activity of the 20S proteasome in cell lysates. Results: Endothelin receptors A and B (ETAR and ETBR, respectively) were found to be expressed in both cell lines, with the RPMI-8226 cells that are considered resistant to BTZ, expressing higher levels of ETBR and in addition secreting ET-1. Treatment of the NCI-H929 cells with ET-1 increased proliferation, while co-incubation of these cells with ET-1 and BTZ decreased BTZ efficacy with concomitant upregulation of 20S proteasomal activity. Si-RNA silencing or chemical blockade of ETBR abrogated the protective effects of ET-1. Finally, data suggest that the predominant signaling pathway involved in ET-1/ETBR-induced BTZ resistance in MM cells may be the MAPK pathway. Conclusion: Our data suggest a possible role of the ET-1/ETBR axis in regulating the sensitivity of MM cells to BTZ. Thus, combining bortezomib with strategies to target the ET-1 axis could prove to be a novel promising therapeutic approach in MM. © 2016, Springer-Verlag Berlin Heidelberg. | en |
dc.language.iso | en | en |
dc.source | Journal of Cancer Research and Clinical Oncology | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84982136539&doi=10.1007%2fs00432-016-2216-2&partnerID=40&md5=8b55c3c89fc41ff8e84df4d96a28a3e1 | |
dc.subject | bortezomib | en |
dc.subject | cyclo(dextro tryptophyl dextro aspartylprolyl dextro valylleucyl) | en |
dc.subject | endothelin 1 | en |
dc.subject | endothelin A receptor | en |
dc.subject | endothelin B receptor | en |
dc.subject | mitogen activated protein kinase | en |
dc.subject | n (2,6 dimethylpiperidinocarbonyl) 4 methylleucyl dextro (1 methoxycarbonyltryptophanyl) dextro norleucine | en |
dc.subject | phosphatidylinositol 3 kinase | en |
dc.subject | bortezomib | en |
dc.subject | cyclo(Trp-Asp-Pro-Val-Leu) | en |
dc.subject | cyclopeptide | en |
dc.subject | endothelin 1 | en |
dc.subject | endothelin A receptor | en |
dc.subject | endothelin A receptor antagonist | en |
dc.subject | endothelin B receptor | en |
dc.subject | phosphatidylinositol 3 kinase | en |
dc.subject | proteasome | en |
dc.subject | ubiquitin | en |
dc.subject | Article | en |
dc.subject | cell proliferation | en |
dc.subject | drug efficacy | en |
dc.subject | drug mechanism | en |
dc.subject | drug resistance | en |
dc.subject | enzyme linked immunosorbent assay | en |
dc.subject | gene silencing | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | multiple myeloma cell line | en |
dc.subject | priority journal | en |
dc.subject | upregulation | en |
dc.subject | drug resistance | en |
dc.subject | enzymology | en |
dc.subject | metabolism | en |
dc.subject | multiple myeloma | en |
dc.subject | signal transduction | en |
dc.subject | tumor cell line | en |
dc.subject | Bortezomib | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Drug Resistance, Neoplasm | en |
dc.subject | Endothelin A Receptor Antagonists | en |
dc.subject | Endothelin-1 | en |
dc.subject | Humans | en |
dc.subject | MAP Kinase Signaling System | en |
dc.subject | Multiple Myeloma | en |
dc.subject | Peptides, Cyclic | en |
dc.subject | Phosphatidylinositol 3-Kinases | en |
dc.subject | Proteasome Endopeptidase Complex | en |
dc.subject | Receptor, Endothelin A | en |
dc.subject | Receptor, Endothelin B | en |
dc.subject | Ubiquitin | en |
dc.subject | Springer Verlag | en |
dc.title | Endothelin-1 (ET-1) induces resistance to bortezomib in human multiple myeloma cells via a pathway involving the ETB receptor and upregulation of proteasomal activity | en |
dc.type | journalArticle | en |