ArticleExperimental hematology2013
Combination chemotherapy increases cytotoxicity of multiple myeloma cells by modification of nuclear factor (NF)-κB activity.
Article in Experimental hematology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Predictive role of levels of soluble interleukin-2 receptor and C-reactive protein in selecting autologous PBSC transplantation for lymphoma.Bone marrow transplantation · 2015Trial
- A phase I first-in-man study to investigate the pharmacokinetics and safety of liposomal dexamethasone in patients with progressive multiple myeloma.Drug delivery and translational research · 2023Article
- β-catenin inhibitors ICG-001 and pyrvinium sensitize bortezomib-resistant multiple myeloma cells to bortezomib.Oncology letters · 2022Article
- Pluronic block copolymers enhance the anti-myeloma activity of proteasome inhibitors.Journal of controlled release : official journal of the Controlled Release Society · 2019Article
- Celastrol Attenuates the Invasion and Migration and Augments the Anticancer Effects of Bortezomib in a Xenograft Mouse Model of Multiple Myeloma.Frontiers in pharmacology · 2018Article
- Unlocking the NF-κB Conundrum: Embracing Complexity to Achieve Specificity.Biomedicines · 2017Review
- Thrombotic microangiopathy associated with proteasome inhibitors.Clinical kidney journal · 2015Review
- The novel β2-selective proteasome inhibitor LU-102 decreases phosphorylation of I kappa B and induces highly synergistic cytotoxicity in combination with ibrutinib in multiple myeloma cells.Cancer chemotherapy and pharmacology · 2015Article
- Copper-zinc superoxide dismutase-mediated redox regulation of bortezomib resistance in multiple myeloma.Redox biology · 2015Article
- Portrait of inflammatory response to ionizing radiation treatment.Journal of inflammation (London, England) · 2015Article
- Increased frequency of Mediterranean fever gene variants in multiple myeloma.Oncology letters · 2014Article
- NF-κB transcriptional activity is modulated by FK506-binding proteins FKBP51 and FKBP52: a role for peptidyl-prolyl isomerase activity.The Journal of biological chemistry · 2014Article
- The synergistic repressive effect of NF-κB and JNK inhibitor on the clonogenic capacity of Jurkat leukemia cells.PloS one · 2014Article
- Retrospective comparative study of the effects of dendritic cell vaccine and cytokine-induced killer cell immunotherapy with that of chemotherapy alone and in combination for colorectal cancer.BioMed research international · 2014Article
- The complexity of NF-κB signaling in inflammation and cancer.Molecular cancer · 2013Review
- Scavenger receptor class A member 3 (SCARA3) in disease progression and therapy resistance in multiple myeloma.Leukemia research · 2013Article
- Scytonemin inhibits cell proliferation and arrests cell cycle through downregulating Plk1 activity in multiple myeloma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- Risk factors for pancreatic cancer: underlying mechanisms and potential targets.Frontiers in physiology · 2013Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The nuclear factor (NF)-κB signaling pathway is critical in myeloma cell proliferation, inhibition of apoptosis, and emergence of therapy resistance. The chemotherapeutic drugs, dexamethasone (Dex) and bortezomib (BTZ), are widely used in clinical protocols for multiple myeloma (MM) and inhibit the NF-κB signaling pathway by distinct mechanisms. This study evaluates the efficacy of combination therapy with Dex and BTZ and investigates the mechanistic underpinning of endogenous and therapy-induced NF-κB activation in MM. Human myeloma cells and bone marrow stromal cells (BMSCs) were used in monocultures and cocultures to determine the cytotoxic effects of Dex and/or BTZ. Our results show that combined treatment of Dex with BTZ enhanced direct apoptosis of drug-sensitive and drug-resistant myeloma cells. In the presence of BMSCs, Dex plus BTZ combination inhibited ionizing radiation-induced interleukin 6 secretion from BMSCs and induced myeloma cytotoxicity. Mechanistically, Dex treatment increased IκBα protein and mRNA expression and compensated for BTZ-induced IκBα degradation. Dex plus BTZ combination inhibited basal and therapy-induced NF-κB activity with cytotoxicity in myeloma cells resistant to BTZ. Furthermore, combination therapy downregulated the NF-κB-targeted gene expression of interleukin 6 and manganese superoxide dismutase, which can induce chemo- and radio-resistance in MM. This study provides a mechanistic rationale for combining the NF-κB-targeting drugs Dex and BTZ in myeloma therapy and supports potential combinations of these drugs with radiotherapy and additional chemotherapeutic drugs for clinical benefit in MM.
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