Pharmacodynamic mechanisms of anti-inflammatory drugs on the chemosensitization of multidrug-resistant cancers and the p
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Inflammopharmacology
REVIEW
Pharmacodynamic mechanisms of anti‑inflammatory drugs on the chemosensitization of multidrug‑resistant cancers and the pharmacogenetics effectiveness Neda Gholamian Dehkordi1 · Seyed Abbas Mirzaei2 · Fatemeh Elahian3 Received: 6 August 2020 / Accepted: 27 September 2020 © Springer Nature Switzerland AG 2020
Abstract 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. Keywords Anti-inflammatory agents · BCRP · Cancer · NSAID · Glucocorticoids · Multidrug resistance · MDR promoters · MDR1 · MRP · Pharmacogenetics Abbreviations ABC transporters ATP-binding cassette transporters ABCC ATP-binding cassette transporters sub-family C ABCA ATP-binding cassette transporters sub-family A Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10787-020-00765-9) contains supplementary material, which is available to authorized users. * Fatemeh Elahian [email protected]; [email protected] 1
Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
2
Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
3
Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
ABCG ATP-binding cassette transporters sub-family G AC Adenylyl cyclase AP-1,2 Activating protein-1 and 2 BCRP Breast cancer resistance protein C/EBP CCAAT-enhancer-binding proteins COX Cyclooxygenase CRE CAMP response element CYP3A4 Cytochrome P450 3A4 ERE Estrogen response element FKBP51 FK506 binding protein 5-FU 5-Fluorouracil γ-GCSh γ-Glutamylcystein synthetase heavy subunit G-protein Guanosine tri
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