Expression analysis of Akirin-2, NFκB-p65 and β-catenin proteins in imatinib resistance of chronic myeloid leukemia

Karabay, Arzu Zeynep; Koç, Aslı; Özkan, Tülin; Hekmatshoar, Yalda; Güneş, Buket Altınok; Sunguroğlu, Asuman; Büyükbingöl, Zeliha; Atalay, Arzu; Aktan, Fügen

doi:10.1080/10245332.2018.1488795

Cited by 16 publications

(9 citation statements)

References 30 publications

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“…Doxorubicin increased p50 (Figure 3c), p65 (Figure 3d), and-to a lesser extent-c-Rel ( Figure S6) binding to target DNA sequences. In accordance with previous evidence found in Reference [39], p50, p65, and c-Rel binding activity was reduced by CURC-SLN and CURC-CS-SLN (Figure 3c,d; Figure S6). Of note, CURC-loaded SLNs also reduced the basal activity of p50 and p65 in the absence of doxorubicin, suggesting particularly strong and specific effects of CURC in inhibiting this dimer.…”

Section: Curc-loaded Slns Decrease Pgp Transcription By Reducing Intrsupporting

confidence: 93%

“…Intracellular ROS can mediate the activation of several transcription factors. Among these redox-sensitive factors, HIF-1α [33,37] and NF-kB [38,39] are well known transcriptional inducers of mdr1 gene. In MDA-MB-231 cells, HIF-1α activity was increased by doxorubicin, as already reported for other cell types [33], but neither free CURC nor CURC-loaded SLNs affected its activity in doxorubicin-treated and untreated cells ( Figure S5).…”

Section: Curc-loaded Slns Decrease Pgp Transcription By Reducing Intrmentioning

confidence: 99%

“…NF-kB is a multimeric transcription factor, whose components (e.g., p50, p65, p52, Rel-A, and c-Rel) form heterodimers characterized by different transcriptional effects [40,41]. Specifically, p65 has been described as binding the mdr1 promoter and activating the transcription of Pgp [39]. p50/p65 dimer is sequestered in cytoplasm in an inactive form by the inhibitor-kB-α (IkB-α).…”

Section: Curc-loaded Slns Decrease Pgp Transcription By Reducing Intrmentioning

confidence: 99%

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Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells

et al. 2020

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Multidrug resistance (MDR) is a critical hindrance to the success of cancer chemotherapy. The main thing responsible for MDR phenotypes are plasma-membranes associated with adenosine triphosphate (ATP) Binding Cassette (ABC) drug efflux transporters, such as the P-glycoprotein (Pgp) transporter that has the broadest spectrum of substrates. Curcumin (CURC) is a Pgp inhibitor, but it is poorly soluble and bioavailable. To overcome these limitations, we validated the efficacy and safety of CURC, loaded in biocompatible solid lipid nanoparticles (SLNs), with or without chitosan coating, with the goal of increasing the stability, homogeneous water dispersibility, and cellular uptake. Both CURC-loaded SLNs were 5–10-fold more effective than free CURC in increasing the intracellular retention and toxicity of doxorubicin in Pgp-expressing triple negative breast cancer (TNBC). The effect was due to the decrease of intracellular reactive oxygen species, consequent inhibition of the Akt/IKKα-β/NF-kB axis, and reduced transcriptional activation of the Pgp promoter by p65/p50 NF-kB. CURC-loaded SLNs also effectively rescued the sensitivity to doxorubicin against drug-resistant TNBC tumors, without signs of systemic toxicity. These results suggest that the combination therapy, based on CURC-loaded SLNs and doxorubicin, is an effective and safe approach to overcome the Pgp-mediated chemoresistance in TNBC.

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Section: Curc-loaded Slns Decrease Pgp Transcription By Reducing Intrsupporting

confidence: 93%

Section: Curc-loaded Slns Decrease Pgp Transcription By Reducing Intrmentioning

confidence: 99%

Section: Curc-loaded Slns Decrease Pgp Transcription By Reducing Intrmentioning

confidence: 99%

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Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells

et al. 2020

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“…Akirin2 dysregulation has also been shown in several rat tumor cell lines 17 – 19 . Akirin2 is upregulated in human primary glioblastomas, and confers chemoresistance to glioblastomas and imatinib resistance to chronic myeloid leukemia 20 , 21 . However, whether Akirin2 promotes angiogenesis, or has other functions in CCA warrants further investigation.…”

Section: Introductionmentioning

confidence: 99%

Akirin2 is modulated by miR-490-3p and facilitates angiogenesis in cholangiocarcinoma through the IL-6/STAT3/VEGFA signaling pathway

Leng

Kang

et al. 2019

Cell Death Dis

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Akirin2 is a key regulator of embryonic development and the innate immunity response. However, this regulator’s role in tumorigenesis especially in cholangiocarcinoma (CCA) development has not been thoroughly elucidated to date. In the current work, we used RT-qPCR, western blot analysis, and immunohistochemistry (IHC) to explore the expression level of Akirin2, and the relationship between Akirin2 levels and clinicopathological characteristics was evaluated. The biological functions of Akirin2 were examined in vitro and in vivo by using a lentiviral vector system. Luciferase reporter assays were applied to detect the direct binding relationship between the 3′-UTR of Akirin2 mRNA and miR-490-3p. The results showed that Akirin2 was overexpressed in CCA and this upregulation was associated with a shorter overall survival. Silencing or overexpressing Akirin2 by lentiviral approaches significantly influenced CCA cell proliferation, migration, invasion, and angiogenesis. An in vivo tumor model further validated the oncogenic effect of Akirin2 on CCA cell growth, metastasis, and angiogenesis. Mechanistic studies demonstrated that Akirin2 induced angiogenesis by increasing the expression of VEGFA by activating the IL-6/STAT3 signaling pathway. Akirin2 promoted cell migratory and invasive potential by affecting the epithelial–mesenchymal transition (EMT) process. In addition, Akirin2 expression was negatively controlled by miR-490-3p in CCA cells, and miR-490-3p attenuated cell migration and angiogenesis in CCA cells by silencing Akirin2. Taken together, the data indicated that Akirin2 could be regulated by miR-490-3p at the posttranscriptional level and facilitate CCA cell progression via the IL-6/STAT3/VEGFA signaling pathway. The present study may expedite the development of novel therapeutic strategies for CCA.

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“…Nuclear beta-catenin, NFκB-p65 and Akirin-2 levels increase in cells with imatinib resistance. Therefore, targeting Akirin-2, NF-κB and beta-catenin genes may provide an opportunity to treat imatinib resistant CML [ 109 ].…”

Section: Targeting Wnt Signaling For Therapeutic Treatment Of Cancermentioning

confidence: 99%

The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy

et al. 2021

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Wnt signaling was initially recognized to be vital for tissue development and homeostasis maintenance. Further studies revealed that this pathway is also important for tumorigenesis and progression. Abnormal expression of signaling components through gene mutation or epigenetic regulation is closely associated with tumor progression and poor prognosis in several tissues. Additionally, Wnt signaling also influences the tumor microenvironment and immune response. Some strategies and drugs have been proposed to target this pathway, such as blocking receptors/ligands, targeting intracellular molecules, beta-catenin/TCF4 complex and its downstream target genes, or tumor microenvironment and immune response. Here we discuss the roles of these components in Wnt signaling pathway in tumorigenesis and cancer progression, the underlying mechanisms that is responsible for the activation of Wnt signaling, and a series of drugs targeting the Wnt pathway provide multiple therapeutic values. Although some of these drugs exhibit exciting anti-cancer effect, clinical trials and systematic evaluation should be strictly performed along with multiple-omics technology.

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Expression analysis of Akirin-2, NFκB-p65 and β-catenin proteins in imatinib resistance of chronic myeloid leukemia

Abstract: We show for the first time that Akirin-2 can be a novel biomarker in imatinib resistance. Targeting Akirin-2, NFκB and β-catenin genes may provide an opportunity to overcome imatinib resistance in CML.

Cited by 16 publications

References 30 publications

Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells

Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells

Akirin2 is modulated by miR-490-3p and facilitates angiogenesis in cholangiocarcinoma through the IL-6/STAT3/VEGFA signaling pathway

The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy

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