Downregulation of NPM reverses multidrug resistance in human hepatoma cells via inhibition of P-glycoprotein expression

Luo, Fei; Li, Huiyu; Liang, Jianfang; Jia, Hong-Ti; Li, Xiaoyü; Xiao, Hong; He, Xue-Hua; He, Junqi; Tian, Yanzhang; Zhao, Hongguang

doi:10.3892/mmr.2017.6246

Cited by 5 publications

(6 citation statements)

References 51 publications

(55 reference statements)

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“…Nuclear factor-κB is a master regulator of inflammation [ 58 ]. Targeting NPM may provide a novel and effective method of reversing the effects of multidrug resistance, and this protein may be a potential adjuvant for tumor chemotherapy [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of NPM, GSTA3, and GNMT in mouse liver following long-term in vivo irradiation by means of uranium tailings

Liang

et al. 2018

Bioscience Reports

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Uranium tailings (UT) are formed as a byproduct of uranium mining and are of potential risk to living organisms. In the present study, we sought to identify potential biomarkers associated with chronic exposure to low dose rate γ radiation originating from UT. We exposed C57BL/6J mice to 30, 100, or 250 μGy/h of gamma radiation originating from UT samples. Nine animals were included in each treatment group. We observed that the liver central vein was significantly enlarged in mice exposed to dose rates of 100 and 250 μGy/h, when compared with nonirradiated controls. Using proteomic techniques, we identified 18 proteins that were differentially expressed (by a factor of at least 2.5-fold) in exposed animals, when compared with controls. We chose glycine N-methyltransferase (GNMT), glutathione S-transferase A3 (GSTA3), and nucleophosmin (NPM) for further investigations. Our data showed that GNMT (at 100 and 250 μGy/h) and NPM (at 250 μGy/h) were up-regulated, and GSTA3 was down-regulated in all of the irradiated groups, indicating that their expression is modulated by chronic gamma radiation exposure. GNMT, GSTA3, and NPM may therefore prove useful as biomarkers of gamma radiation exposure associated with UT. The mechanisms underlying those changes need to be further studied.

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Section: Discussionmentioning

confidence: 99%

Differential expression of NPM, GSTA3, and GNMT in mouse liver following long-term in vivo irradiation by means of uranium tailings

Liang

et al. 2018

Bioscience Reports

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“…Initially, the activation of ABC transporter proteins was observed upon exposure to conventional chemotherapy agents such as doxorubicin, cisplatin, and 5-fluorouracil (5-FU) as their common substrates [39][40][41]. In the development of molecular therapy, sorafenib was shown to modulate multidrug resistance caused by chemotherapy.…”

Section: Drug Efflux: Abc Transporters Familymentioning

confidence: 99%

Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity

Cabral

Tiribelli

Sukowati

2020

Cancers

110

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Despite advances in biomedicine, the incidence and the mortality of hepatocellular carcinoma (HCC) remain high. The majority of HCC cases are diagnosed in later stages leading to the less than optimal outcome of the treatments. Molecular targeted therapy with sorafenib, a dual-target inhibitor targeting the serine-threonine kinase Raf and the tyrosine kinases VEGFR/PDGFR, is at present the main treatment for advanced-stage HCC, either in a single or combinatory regimen. However, it was observed in a large number of patients that its effectiveness is hampered by drug resistance. HCC is highly heterogeneous, within the tumor and among individuals, and this influences disease progression, classification, prognosis, and naturally cellular susceptibility to drug resistance. This review aims to provide an insight on how HCC heterogeneity influences the different primary mechanisms of chemoresistance against sorafenib including reduced drug intake, enhanced drug efflux, intracellular drug metabolism, alteration of molecular targets, activation/inactivation of signaling pathways, changes in the DNA repair machinery, and negative balance between apoptosis and survival of the cancer cells. The diverse variants, mutations, and polymorphisms in molecules and their association with drug response can be a helpful tool in treatment decision making. Accordingly, the existence of heterogeneous biomarkers in the tumor must be considered to strengthen multi-target strategies in patient-tailored treatment.

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“…102 The downregulation of NPM1 expression markedly reversed the effects of multidrug resistance (MDR) in human hepatoma cells via inhibition of P-glycoprotein expression. 101 To date, relatively little is known about the role of NPM1 overexpression in hematologic malignancies. A recent study identified mutated chronic lymphocytic leukemia cells that were characterized by a MYC-related overexpression of NPM1 and ribosome-associated components.…”

Section: Npm1 Translocations In Lymphomasmentioning

confidence: 99%

“…Modulation of NPM1 expression occurred within CRC cells, affecting cellular viability, p53-dependent senescence, and cell-cycle progression, indicating that NPM1 may play a fundamental role in colorectal carcinogenesis. 97 The high expression of NPM1 has also been reported to link to gradient drug resistance in bladder cancer, 99,100 lung cancer, 15 hepatoma carcinoma, 101 and breast carcinoma. 102 The downregulation of NPM1 expression markedly reversed the effects of multidrug resistance (MDR) in human hepatoma cells via inhibition of P-glycoprotein expression.…”

Section: Npm1 Overexpression In Solid Tumors and Hematologic Malignanmentioning

confidence: 99%

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Nucleophosmin1 (NPM1) abnormality in hematologic malignancies, and therapeutic targeting of mutant NPM1 in acute myeloid leukemia

Chen

2020

Therapeutic Advances in Hematology

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Nucleophosmin ( NPM1) is an abundant nucleolar protein that is implicated in a variety of biological processes and in the pathogenesis of several human malignancies. For hematologic malignancies, approximately one-third of anaplastic large-cell non-Hodgkin’s lymphomas were found to express a fusion between NPM1 and the catalytic domain of anaplastic lymphoma receptor tyrosine kinase. About 50–60% of acute myeloid leukemia patients with normal karyotype carry NPM1 mutations, which are characterized by cytoplasmic dislocation of the NPM1 protein. Nevertheless, NPM1 is overexpressed in various hematologic and solid tumor malignancies. NPM1 overexpression is considered a prognostic marker of recurrence and progression of cancer. Thus, NPM1 abnormalities play a critical role in several types of hematologic malignancies. This has led to intense interest in the development of an NPM1 targeting strategy for cancer therapy. The aim of this review is to summarize present knowledge on NPM1 origin, pathogenesis, and therapeutic interventions in hematologic malignancies.

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Downregulation of NPM reverses multidrug resistance in human hepatoma cells via inhibition of P-glycoprotein expression

Cited by 5 publications

References 51 publications

Differential expression of NPM, GSTA3, and GNMT in mouse liver following long-term in vivo irradiation by means of uranium tailings

Differential expression of NPM, GSTA3, and GNMT in mouse liver following long-term in vivo irradiation by means of uranium tailings

Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity

Nucleophosmin1 (NPM1) abnormality in hematologic malignancies, and therapeutic targeting of mutant NPM1 in acute myeloid leukemia

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