ArticleLaboratory investigation; a journal of technical methods and pathology2019
Overexpression of HIF-1α contributes to melphalan resistance in multiple myeloma cells by activation of ERK1/2, Akt, and NF-κB.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 41 citations in OpenAlex.
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- Overexpression of miR-29a and miR-29b is involved in imatinib resistance via abrogated NF1 expression and increased ERK1/2 activation in chronic myeloid leukemia cells.Medical oncology (Northwood, London, England) · 2025Article
- Oxaliplatin and 5-fluorouracil promote epithelial-mesenchymal transition via activation of KRAS/ERK/NF-κB pathway in KRAS-mutated colon cancer cells.Molecular and cellular biochemistry · 2025Article
- MDM2 inhibitors induce apoptosis by suppressing MDM2 and enhancing p53, Bax, Puma and Noxa expression levels in imatinib‑resistant chronic myeloid leukemia cells.Biomedical reports · 2025Article
- Mimicking Retinoblastoma Treatment With Repeated Topotecan or Melphalan Develops Cross-Resistance to Classic Agents But Not to Repurposed Drugs.Investigative ophthalmology & visual science · 2024Article
- Pathways to therapy resistance: The sheltering effect of the bone marrow microenvironment to multiple myeloma cells.Heliyon · 2024Review
- Curcumin in treatment of hematological cancers: Promises and challenges.Journal of traditional and complementary medicine · 2024Review
- HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.Genes & diseases · 2024Review
- Bim downregulation by activation of NF-κB p65, Akt, and ERK1/2 is associated with adriamycin and dexamethasone resistance in multiple myeloma cells.Clinical and experimental medicine · 2023Article
- Osteocyte-derived exosomes confer multiple myeloma resistance to chemotherapy through acquisition of cancer stem cell-like features.Leukemia · 2023Article
- Activation of ERK1/2 by MOS and TPL2 leads to dasatinib resistance in chronic myeloid leukaemia cells.Cell proliferation · 2023Article
- SETDB1 induces lenalidomide resistance in multiple myeloma cells via epithelial‑mesenchymal transition and PI3K/AKT pathway activation.Experimental and therapeutic medicine · 2023Article
- Article
- Role of NF-κB Signaling in the Interplay between Multiple Myeloma and Mesenchymal Stromal Cells.International journal of molecular sciences · 2023Review
- Targeting hypoxia in solid and haematological malignancies.Journal of experimental & clinical cancer research : CR · 2022Review
- Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells.International journal of molecular sciences · 2022Article
- Blockade of p38 MAPK overcomes AML stem cell line KG1a resistance to 5-Fluorouridine and the impact on miRNA profiling.PloS one · 2022Article
- Characterization of cannabinoid receptors expressed in Ewing sarcoma TC-71 and A-673 cells as potential targets for anti-cancer drug development.Life sciences · 2021Article
- Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma.Cellular and molecular life sciences : CMLS · 2021Review
- Pharmacodynamic mechanisms of anti-inflammatory drugs on the chemosensitization of multidrug-resistant cancers and the pharmacogenetics effectiveness.Inflammopharmacology · 2021Review
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7 authors at 1 institution in 1 country.
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Abstract
Multiple myeloma (MM) commonly displays multidrug resistance and is associated with poor prognosis. Therefore, it is important to identify the mechanisms by which MM cells develop multidrug resistance. Our previous study showed that multidrug resistance is correlated with overexpression of multidrug resistance protein 1 (MDR1) and Survivin, and downregulation of Bim expression in melphalan-resistant RPMI8226/L-PAM cells; however, the underlying mechanism of multidrug resistance remains unclear. In the present study, we investigated the mechanism of multidrug resistance in melphalan-resistant cells. We found that RPMI8226/L-PAM and ARH-77/L-PAM cells showed increased phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and Akt, and nuclear localization of nuclear factor κB (NF-κB). The combination of ERK1/2, Akt, and NF-κB inhibitors with melphalan reversed melphalan resistance via suppression of Survivin expression and enhanced Bim expression in melphalan-resistant cells. In addition, RPMI8226/L-PAM and ARH-77/L-PAM cells overexpressed hypoxia-inducible factor 1α (HIF-1α) via activation of ERK1/2, Akt, and NF-κB. Moreover, suppression of HIF-1α by echinomycin or HIF-1α siRNA resensitized RPMI8226/L-PAM cells to melphalan through downregulation of Survivin expression and upregulation of Bim expression. These results indicate that enhanced Survivin expression and decreased Bim expression by HIF-1α via activation of ERK1/2, Akt, and NF-κB play a critical role in melphalan resistance. Our findings suggest that HIF-1α, ERK1/2, Akt, and NF-κB inhibitors are potentially useful as anti-MDR agents for the treatment of melphalan-resistant MM.
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