Ability of polymer-bound P-glycoprotein inhibitor ritonavir to overcome multidrug resistance in various resistant neuroblastoma cell lines
Language English Country Great Britain, England Media print
Document type Journal Article
- MeSH
- Acrylamides administration & dosage pharmacology MeSH
- Drug Resistance, Neoplasm MeSH
- Doxorubicin administration & dosage pharmacology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Neuroblastoma drug therapy metabolism MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 antagonists & inhibitors biosynthesis MeSH
- Antineoplastic Combined Chemotherapy Protocols pharmacology MeSH
- Ritonavir administration & dosage pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Drug Synergism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acrylamides MeSH
- Doxorubicin MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Browser
- ATP Binding Cassette Transporter, Subfamily B, Member 1 MeSH
- Ritonavir MeSH
Polymer prodrugs can considerably improve the treatment of tumors with multidrug resistance, often caused by overexpression of P-glycoprotein (P-gp). Here, we present the effect of the N-(2-hydroxypropyl) methacrylamide-based polymer conjugate with P-gp inhibitor ritonavir (RIT) on the increase of free doxorubicin (DOX) and polymer-bound DOX cytotoxicity in the human neuroblastoma 4 cell line and its resistant clones to different cytostatics. The increase in cytotoxicity after polymer-RIT conjugate pretreatment was higher for the lines overexpressing P-gp and less pronounced for those with decreased P-gp levels. Moreover, the effect of polymer conjugate containing inhibitor and DOX on the same polymer chain was lower than that of two individual polymer conjugates used sequentially. In conclusion, the polymer-RIT conjugate can significantly increase the cytotoxicity of free DOX and polymer-DOX conjugates in cells with various multidrug resistance origins and can thus be considered a suitable therapeutic enhancer of polymer prodrugs.
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