Pharmacodynamic mechanisms of anti-inflammatory drugs on the chemosensitization of multidrug-resistant cancers and the pharmacogenetics effectiveness.

Autor: Gholamian Dehkordi, Neda, Mirzaei, Seyed Abbas, Elahian, Fatemeh
Předmět:
Zdroj: Inflammopharmacology; Feb2021, Vol. 29 Issue 1, p49-74, 26p
Abstrakt: Drug resistance as a remarkable issue in cancer treatment is associated with inflammation which occurs through complex chemical reactions in the tumor microenvironment. Recent studies have implicated that glucocorticoids and NSAIDs are mainly useful combinations for inflammatory response modulation in chemotherapeutic protocols for cancer treatment. Immunosuppressive actions of glucocorticoids and NSAIDs are mainly mediated by the transrepression or activation regulation of inflammatory genes with different DNA-bound transcription factors including AP-1, NFAT, NF-κB, STAT and also, varying functions of COX enzymes in cancer cells. Interestingly, many investigations have proved the benefits of these anti-inflammatory agents in the quenching of multidrug resistance pathways. Numerous analyses on the ABC transporter promoters showed conserved nucleotide sequences with several DNA response elements that participate in transcriptional regulation. Furthermore, genetic variations in nucleotide sequences of membrane transporters were strongly associated with changes in these transporters' expression or function and a substantial impact on systemic drug exposure and toxicity. It appeared that several polymorphisms in MDR transporter genes especially MDR1 have influenced the regulatory mechanisms and explained differences in glucocorticoid responses. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index