MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance

Yan, Zi‐Xun; Zheng, Zhong; Xue, Wen; Zhao, Mingzhe; Fei, Xiaochun; Wu, Lili; Huang, Li‐Min; Lebœuf, Christophe; Janin, Anne; Wang, Li; Zhao, Wei‐Li

doi:10.1155/2015/197241

Cited by 23 publications

(24 citation statements)

References 24 publications

(35 reference statements)

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“…Acquired drug resistance is an significant obstacle that impairs the success of cancer treatment. Isogenic Dox-resistant sublines were developed as previously reported 14,18 Figure 4C), but also increased apoptosis of the Dox-resistant cells ( Figure 4D).…”

Section: Dox-ncs Inhibited P-gp Induction and Induced Dox-resistant Csupporting

confidence: 63%

“…Accumulating evidence has shown that Dox-treatment could induce tumor cell P-gp expression, resulting in increased drug excretion and multidrug resistance. 18,19 Compared with Dox, Dox-NCs inhibited P-gp expression ( Figure 4A). As the mechanism of action, cytoplasmic ATP concentration was significantly lower, after 48 hours incubation, in Dox-NCs-treated cells (Jurkat 0.63±0.11 nmol/10 6 cells, Namalwa 0.71±0.29 nmol/10 6 cells), when compared with Dox-treated cells (Jurkat 1.34±0.11 nmol/10 6 cells, Namalwa 1.66±0.22 nmol/10 6 cells, P,0.05, Figure 4B).…”

Section: Dox-ncs Inhibited P-gp Induction and Induced Dox-resistant Cmentioning

confidence: 99%

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Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity

Fang¹,

Wang²,

Dou³

et al. 2018

IJN

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PurposeCardiac side effects of doxorubicin (Dox) have limited its clinical application. The aim of this study was to explore new Dox-loaded dextran-based nano-carriers (NCs) in efficiently targeting tumor growth with less cardiac toxicity.MethodsInspired by recent reports that polymeric NCs could function as sustained, controlled and targeted drug delivery systems, we developed Dox-loaded NCs which displayed a 2-fold release ratio of Dox in the mimic tumor site condition (pH 5.0 with 10 mM glutathione, GSH) as much as that in systemic circulation condition (pH 7.4).ResultsLymphoma cells treated with Dox-NCs had significantly higher intracellular Dox concentrations and more apoptotic induction, with lower P-gp expression, when compared with those treated with Dox alone. The identified mechanism of action, apoptosis, was triggered through survivin reduction and caspase-3 activation. Even in the Dox-resistant cells, Dox-NCs could significantly inhibit cell growth and induce apoptosis. In murine lymphoma xenograft models, Dox-NCs also remarkably significantly retarded tumor growth, assessed by murine weight, and demonstrated less cytotoxicity. Noticeably, apoptotic myocardial cells were decreased in the Dox-NCs-treated group, when compared with the control group, which was consistent with low intracellular Dox concentration in the cardiac cell line H9C2.ConclusionDox-NCs showed an anti-lymphoma effect with reduced cardiac toxicity in both in vivo and in vitro models and, therefore, could be a potential therapeutic agent in the treatment of lymphoma.

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Section: Dox-ncs Inhibited P-gp Induction and Induced Dox-resistant Csupporting

confidence: 63%

Section: Dox-ncs Inhibited P-gp Induction and Induced Dox-resistant Cmentioning

confidence: 99%

Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity

Fang¹,

Wang²,

Dou³

et al. 2018

IJN

Self Cite

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“…As mentioned above, miR-19, which belongs to the miR-17-92 cluster, controlled multiple regulators ( PP2A , PRKAA1 , BIM , and PTEN ) of PI3K signaling which resulted in increased phosphorylation of AKT and the ribosomal S6 protein, which subsequently promoted survival of T-ALL cells [ 44 ]. Additionally, miR-181a could induce chemoresistance in Jurkat T-ALL cells through activating AKT, which will be discussed in detail later [ 59 ]. Moreover, luciferase assay experiments showed that miR-19 directly repressed the expression of CYLD , which plays a predominant role in the negative regulation of NF-κB, inducing activation of the NF-κB downstream program [ 45 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA expression and activity in T-cell acute lymphoblastic leukemia

2017

Oncotarget

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T-cell acute lymphoblastic leukemia (T-ALL) is a lymphoid malignancy caused by the oncogenic transformation of immature T-cell progenitors. Many biologically relevant genetic and epigenetic alterations have been identified as driving factors for this transformation. Recently, microRNAs (miRNAs) have been shown to influence various leukemias, including T-ALL. Aberrant expression of miRNAs can function as either oncogenes or tumor suppressors in T-ALL through the regulation of cell migration, invasion, proliferation, apoptosis, and chemoresistance. This occurs by targeting key signaling pathways or transcriptional factors that play a critical role in T-ALL pathology and progression. Different miRNA expression profiles have been linked to specific genetic subtypes of human T-ALL. Furthermore, miRNAs can also act as independent prognostic factors to predict clinical outcomes for T-ALL patients. In the current review, we will focus on the role of miRNAs in the development and progression of T-ALL.

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“…3A and B, the expression of p65 was decreased significantly in celecoxib-treated Jurkat and Hut-78 cells. It is well-known that the NF-κB P65 subunit participates in activating various downstream genes associated with the regulation of apoptosis and induction of MDR (6)(7)(8). Several studies have revealed that Bcl-2 may suppress the activity of multiple pro-apoptotic proteins by binding with P65 (3,6).…”

Section: Celecoxib Inhibits the Expression Of The Mdr-associated Protmentioning

confidence: 99%

“…It is well-known that the NF-κB P65 subunit participates in activating various downstream genes associated with the regulation of apoptosis and induction of MDR (6)(7)(8). Several studies have revealed that Bcl-2 may suppress the activity of multiple pro-apoptotic proteins by binding with P65 (3,6). Additionally, previous studies also confirmed that the majority of the MDR-associated proteins, including P-gp and MRP1, are positively regulated by the NF-κB pathway, and that blockade of the NF-κB pathway may suppress their expression (6,7).…”

Section: Celecoxib Inhibits the Expression Of The Mdr-associated Protmentioning

confidence: 99%

Celecoxib enhances sensitivity to chemotherapy drugs of T‑cell lymphoma

Yang

Zhao

et al. 2018

Oncol Lett

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Abstract. Celecoxib is a newly-identified nonsteroidal anti-inflammatory drug, which has been used to treat fever in clinical practice. Celecoxib has been demonstrated to suppress the viability of various human tumor cells. However, the effect of celecoxib on response of T-cell lymphoma to chemotherapy agents remains unclear. The aim of the present study was to investigate the effect of celecoxib on chemosensitivity of human T-cell lymphoma, and to address the underlying mechanism of action. The cytotoxicity of CDDP, epirubicin and VCR on Jurkat and Hut-78 cells treated with celecoxib was assessed by MTT assay, and the half-maximal inhibitory concentration (IC 50 ) value was calculated by Origin 75 software. The effect of celecoxib on apoptosis and intracellular concentration of Rhodamine-123 in Jurkat and Hut-78 cells was analyzed by flow cytometry. The expression of transcription factor p65 (p65), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) at mRNA and protein levels were detected by reverse transcription quantitative polymerase chain reaction and western blotting, respectively. Proliferation suppression rates and apoptosis levels were significantly increased in Jurkat and Hut-78 cells combined with celecoxib compared with those without celecoxib, when treated with CDDP, epirubicin and VCR. The IC 50 values of the chemotherapy agents were lower in Jurkat and Hut-78 cells treated with celecoxib compared with those that were not.The apoptosis level, expression of Bax and the intracellular concentration of Rhodamine-123 were increased, whereas the expression of p65, Bcl-2, MDR1 and MRP1 were decreased, in celecoxib-treated Jurkat and Hut-78 cells compared with those without celecoxib treatment. These results indicated that celecoxib may enhance the sensitivity of T-cell lymphoma to chemotherapy drugs by inhibiting the expression of multidrug resistance (MDR)-associated proteins via downregulating the activity of the nuclear factor-κB signaling pathway, suggesting that celecoxib may improve the curative effect of chemotherapy drugs in T-cell lymphoma.

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MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance

Cited by 23 publications

References 24 publications

Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity

Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity

MicroRNA expression and activity in T-cell acute lymphoblastic leukemia

Celecoxib enhances sensitivity to chemotherapy drugs of T‑cell lymphoma

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