Dexamethasone enhances the antitumor efficacy of Gemcitabine by glucocorticoid receptor signaling

References

• Petrioli R, Roviello G, Fiaschi AI, Laera L, Marrelli D, Roviello F and Francini E. Gemcitabine, oxaliplatin, and capecitabine (GEMOXEL) compared with gemcitabine alone in metastatic pancreatic cancer: a randomized phase II study. Cancer Chemother Pharmacol. 2015;75:683–690. doi:10.1007/s00280-015-2683-1.
   PubMed Web of Science ®Google Scholar
• O’Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, et al. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014;32:3840–3847. doi:10.1200/JCO.2014.55.2984.
   PubMed Web of Science ®Google Scholar
• Morschhauser F, Depil S, Jourdan E, Wetterwald M, Bouabdallah R, Marit G, Solal-Celigny P, Sebban C, Coiffier B, Chouaki N, et al. Phase II study of gemcitabine–dexamethasone with or without cisplatin in relapsed or refractory mantle cell lymphoma. Ann Oncol. 2007;18:370–375. doi:10.1093/annonc/mdl395.
   PubMed Web of Science ®Google Scholar
• Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold C, Palmer MC, Gregor A, et al. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2000;18:122–130. doi:10.1200/JCO.2000.18.1.122.
   PubMed Web of Science ®Google Scholar
• von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18:3068–3077. doi:10.1200/JCO.2000.18.17.3068.
   PubMed Web of Science ®Google Scholar
• Pfisterer J, Plante M, Vergote I, Du Bois A, Hirte H, Lacave AJ, Wagner U, Stähle A, Stuart G, Kimmig R, et al. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J Clin Oncol. 2006;24:4699–4707. doi:10.1200/JCO.2006.06.0913.
   PubMed Web of Science ®Google Scholar
• de Sousa Cavalcante L, Monteiro G. Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol. 2014;741:8–16. doi:10.1016/j.ejphar.2014.07.041.
   PubMed Web of Science ®Google Scholar
• Mini E, Nobili S, Caciagli B, Landini I, Mazzei T. Cellular pharmacology of gemcitabine. Ann Oncol. 2006;17(Suppl 5):v7–12. doi:10.1093/annonc/mdj941.
   PubMed Web of Science ®Google Scholar
• Wang H, Li M, Rinehart JJ, Zhang R. Dexamethasone as a chemoprotectant in cancer chemotherapy: hematoprotective effects and altered pharmacokinetics and tissue distribution of carboplatin and gemcitabine. Cancer Chemother Pharmacol. 2004;53:459–467. doi:10.1007/s00280-003-0759-9.
   PubMed Web of Science ®Google Scholar
• Wang H, Wang Y, Rayburn ER, Hill DL, Rinehart JJ, Zhang R. Dexamethasone as a chemosensitizer for breast cancer chemotherapy: potentiation of the antitumor activity of adriamycin, modulation of cytokine expression, and pharmacokinetics. Int J Oncol. 2007;30:947–953.
   PubMed Web of Science ®Google Scholar
• Sun N, Ji H, Wang W, Zhu Q, Cao M, Zang Q. Inhibitory effect of dexamethasone on residual Lewis lung cancer cells in mice following palliative surgery. Oncol Lett. 2017;13:356–362. doi:10.3892/ol.2016.5422.
   PubMed Web of Science ®Google Scholar
• Yano A, Fujii Y, Iwai A, Kageyama Y, Kihara K. Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells. Clin Cancer Res. 2006;12:3003–3009. doi:10.1158/1078-0432.CCR-05-2085.
   PubMed Web of Science ®Google Scholar
• Arai Y, Nonomura N, Nakai Y, Nishimura K, Oka D, Shiba M, Nakayama M, Takayama H, Mizutani Y, Miki T, et al. The growth-inhibitory effects of dexamethasone on renal cell carcinoma in vivo and in vitro. Cancer Invest. 2008;26:35–40. doi:10.1080/07357900701638418.
   PubMed Web of Science ®Google Scholar
• Gong H, Jarzynka MJ, Cole TJ, Lee JH, Wada T, Zhang B, Gao J, Song W-C, DeFranco DB, Cheng S-Y, et al. Glucocorticoids antagonize estrogens by glucocorticoid receptor-mediated activation of estrogen sulfotransferase. Cancer Res. 2008;68:7386–7393. doi:10.1158/0008-5472.CAN-08-1545.
   PubMed Web of Science ®Google Scholar
• Lewis KM, Harford-Wright E, Vink R, Ghabriel MN. NK1 receptor antagonists and dexamethasone as anticancer agents in vitro and in a model of brain tumours secondary to breast cancer. Anticancer Drugs. 2013;24:344–354. doi:10.1097/CAD.0b013e32835ef440.
   PubMed Web of Science ®Google Scholar
• Villeneuve J, Galarneau H, Beaudet MJ, Tremblay P, Chernomoretz A, Vallieres L. Reduced glioma growth following dexamethasone or anti-angiopoietin 2 treatment. Brain Pathol. 2008;18:401–414. doi:10.1111/j.1750-3639.2008.00139.x.
   PubMed Web of Science ®Google Scholar
• Bavaresco L, Bernardi A, Braganhol E, Wink MR, Battastini AM. Dexamethasone inhibits proliferation and stimulates ecto-5ʹ-nucleotidase/CD73 activity in C6 rat glioma cell line. J Neurooncol. 2007;84:1–8. doi:10.1007/s11060-007-9342-2.
   PubMed Web of Science ®Google Scholar
• Coimbra M, Rijcken CJ, Stigter M, Hennink WE, Storm G, Schiffelers RM. Antitumor efficacy of dexamethasone-loaded core-crosslinked polymeric micelles. J Control Release. 2012;163:361–367. doi:10.1016/j.jconrel.2012.09.014.
   PubMed Web of Science ®Google Scholar
• Nishimura K, Nonomura N, Satoh E, Harada Y, Nakayama M, Tokizane T, Fukui T, Ono Y, Inoue H, Shin M, et al. Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer. J Natl Cancer Inst. 2001;93:1739–1746. doi:10.1093/jnci/93.22.1739.
   PubMedGoogle Scholar
• Nishimura K, Nonomura N, Yasunaga Y, Takaha N, Inoue H, Sugao H, Yamaguchi S, Ukimura O, Miki T, Okuyama A, et al. Low doses of oral dexamethasone for hormone-refractory prostate carcinoma. Cancer. 2000;89:2570–2576. doi:10.1002/(ISSN)1097-0142.
   PubMed Web of Science ®Google Scholar
• Yuan Y, Zhou X, Ren Y, Zhou S, Wang L, Ji S, Hua M, Li L, Lu W, Zhou T, et al. Semi-mechanism-based pharmacokinetic/pharmacodynamic model for the combination use of dexamethasone and gemcitabine in breast cancer. J Pharm Sci. 2015;104:4399–4408. doi:10.1002/jps.24629.
   PubMed Web of Science ®Google Scholar
• Stringer-Reasor EM, Baker GM, Skor MN, Kocherginsky M, Lengyel E, Fleming GF and Conzen S.D. Glucocorticoid receptor activation inhibits chemotherapy-induced cell death in high-grade serous ovarian carcinoma. Gynecol Oncol. 2015;138:656–662. doi:10.1016/j.ygyno.2015.06.033.
   PubMed Web of Science ®Google Scholar
• Liu L, Xiong X, Shen M, Ru D, Gao P, Zhang X, Huang C, Sun Y, Li H, Duan Y, et al. Co-delivery of triptolide and curcumin for ovarian cancer targeting therapy via mPEG-DPPE/CaP nanoparticle. J Biomed Nanotechnol. 2018;14:1761–1772. doi:10.1166/jbn.2018.2633.
   PubMed Web of Science ®Google Scholar
• Gong JH, Liu XJ, Li Y, Zhen YS. Pingyangmycin downregulates the expression of EGFR and enhances the effects of cetuximab on esophageal cancer cells and the xenograft in athymic mice. Cancer Chemother Pharmacol. 2012;69:1323–1332. doi:10.1007/s00280-012-1827-9.
   PubMed Web of Science ®Google Scholar
• Spoorenberg SM, Deneer VH, Grutters JC, Pulles AE, Voorn GP, Rijkers GT, et al. Pharmacokinetics of oral vs. intravenous dexamethasone in patients hospitalized with community-acquired pneumonia. Br J Clin Pharmacol. 2014;78:78–83. doi:10.1111/bcp.2014.78.issue-1.
   PubMed Web of Science ®Google Scholar
• Gravitz L. Liver cancer. Nature. 2014;516:S1. doi:10.1038/516S1a.
   PubMed Web of Science ®Google Scholar
• Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–1617. doi:10.1056/NEJMra0901557.
   PubMed Web of Science ®Google Scholar
• Zhang C, Wenger T, Mattern J, Ilea S, Frey C, Gutwein P, Altevogt P, Bodenmüller W, Gassler N, Schnabel PA, et al. Clinical and mechanistic aspects of glucocorticoid-induced chemotherapy resistance in the majority of solid tumors. Cancer Biol Ther. 2007;6:278–287. doi:10.4161/cbt.6.2.3652.
   PubMed Web of Science ®Google Scholar
• Pan D, Kocherginsky M, Conzen SD. Activation of the glucocorticoid receptor is associated with poor prognosis in estrogen receptor-negative breast cancer. Cancer Res. 2011;71:6360–6370. doi:10.1158/0008-5472.CAN-11-0362.
   PubMed Web of Science ®Google Scholar
• Gassler N, Zhang C, Wenger T, PA S, Dienemann H, KM D, et al. Dexamethasone-induced cisplatin and gemcitabine resistance in lung carcinoma samples treated ex vivo. Br J Cancer. 2005;92:1084–1088. doi:10.1038/sj.bjc.6602453.
   PubMed Web of Science ®Google Scholar
• Chen Z, Lan X, Wu D, Sunkel B, Ye Z, Huang J, Liu Z, Clinton SK, Jin VX, Wang Q, et al. Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer. Nat Commun. 2015;6:8323. doi:10.1038/ncomms9323.
   PubMed Web of Science ®Google Scholar
• Liu L, Aleksandrowicz E, Schonsiegel F, Groner D, Bauer N, Nwaeburu CC, Zhao Z, Gladkich J, Hoppe-Tichy T, Yefenof E, et al. Dexamethasone mediates pancreatic cancer progression by glucocorticoid receptor, TGFbeta and JNK/AP-1. Cell Death Dis. 2017;8:e3064. doi:10.1038/cddis.2017.455.
   PubMed Web of Science ®Google Scholar
• de Guia RM, Herzig S. How do glucocorticoids regulate lipid metabolism? Adv Exp Med Biol. 2015;872:127–144.
   PubMed Web of Science ®Google Scholar
• Kim IK, Kim BS, Koh CH, Seok JW, Park JS, Shin KS, Bae E-A, Lee G-E, Jeon H, Cho J, et al. Glucocorticoid-induced tumor necrosis factor receptor-related protein co-stimulation facilitates tumor regression by inducing IL-9-producing helper T cells. Nat Med. 2015;21:1010–1017. doi:10.1038/nm.3922.
   PubMed Web of Science ®Google Scholar
• Minchenko DO, Riabovol OO, Tsymbal DO, Ratushna OO, Minchenko OH. Inhibition of IRE1 signaling affects the expression of genes encoded glucocorticoid receptor and some related factors and their hypoxic regulation in U87 glioma cells. Endocr Regul. 2016;50:127–136. doi:10.1515/enr-2016-0014.
   PubMedGoogle Scholar
• Psarra AM, Sekeris CE. Glucocorticoids induce mitochondrial gene transcription in HepG2 cells: role of the mitochondrial glucocorticoid receptor. Biochim Biophys Acta. 2011;1813:1814–1821. doi:10.1016/j.bbamcr.2011.05.014.
   PubMed Web of Science ®Google Scholar
• Mikosz CA, Brickley DR, Sharkey MS, Moran TW, Conzen SD. Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1. J Biol Chem. 2001;276:16649–16654. doi:10.1074/jbc.M010842200.
   PubMed Web of Science ®Google Scholar
• Alam MM, Okazaki K, Nguyen LTT, Ota N, Kitamura H, Murakami S, Shima H, Igarashi K, Sekine H, Motohashi H, et al. Glucocorticoid receptor signaling represses the antioxidant response by inhibiting histone acetylation mediated by the transcriptional activator NRF2. J Biol Chem. 2017;292:7519–7530. doi:10.1074/jbc.M116.773960.
   PubMed Web of Science ®Google Scholar
• Hayden A, Douglas J, Sommerlad M, Andrews L, Gould K, Hussain S, et al. The Nrf2 transcription factor contributes to resistance to cisplatin in bladder cancer. Urol Oncol. 2014;32:806–814. doi:10.1016/j.urolonc.2014.02.006.
   PubMed Web of Science ®Google Scholar
• Chen J, Solomides C, Simpkins F, Simpkins H. The role of Nrf2 and ATF2 in resistance to platinum-based chemotherapy. Cancer Chemother Pharmacol. 2017;79:369–380. doi:10.1007/s00280-016-3225-1.
   PubMed Web of Science ®Google Scholar
• Bialk P, Wang Y, Banas K, Kmiec EB. Functional gene knockout of NRF2 increases chemosensitivity of human lung cancer A549 cells in vitro and in a xenograft mouse model. Mol Ther Oncolytics. 2018;11:75–89. doi:10.1016/j.omto.2018.10.002.
   PubMed Web of Science ®Google Scholar
• Wang XJ, Sun Z, Villeneuve NF, Zhang S, Zhao F, Li Y, Chen W, Yi X, Zheng W, Wondrak GT, et al. Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis. 2008;29:1235–1243. doi:10.1093/carcin/bgn095.
   PubMed Web of Science ®Google Scholar
• Niture SK, Jaiswal AK. Nrf2 protein up-regulates antiapoptotic protein Bcl-2 and prevents cellular apoptosis. J Biol Chem. 2012;287:9873–9886. doi:10.1074/jbc.M111.312694.
   PubMed Web of Science ®Google Scholar
• Niture SK, Jaiswal AK. Nrf2-induced antiapoptotic Bcl-xL protein enhances cell survival and drug resistance. Free Radic Biol Med. 2013;57:119–131. doi:10.1016/j.freeradbiomed.2012.12.014.
   PubMed Web of Science ®Google Scholar
• Xiang Y, Ye W, Huang C, Yu D, Chen H, Deng T, Zhang F, Lou B, Zhang J, Shi K, et al. Brusatol enhances the chemotherapy efficacy of gemcitabine in pancreatic cancer via the Nrf2 signalling pathway. Oxid Med Cell Longev. 2018;2018:2360427. doi:10.1155/2018/2360427.
   PubMed Web of Science ®Google Scholar
• Kiraz Y, Adan A, Kartal Yandim M, Baran Y. Major apoptotic mechanisms and genes involved in apoptosis. Tumour Biol. 2016;37:8471–8486. doi:10.1007/s13277-016-5035-9.
   PubMed Web of Science ®Google Scholar
• Parrish AB, Freel CD, Kornbluth S. Cellular mechanisms controlling caspase activation and function. Cold Spring Harb Perspect Biol. 2013;5:a008672–a008672. doi:10.1101/cshperspect.a008672.
   PubMed Web of Science ®Google Scholar
• Kumar S. Caspase function in programmed cell death. Cell Death Differ. 2007;14:32–43. doi:10.1038/sj.cdd.4402060.
   PubMed Web of Science ®Google Scholar