scholarly journals Resistin induces multidrug resistance in myeloma by inhibiting cell death and upregulating ABC transporter expression

Haematologica ◽  
2017 ◽  
Vol 102 (7) ◽  
pp. 1273-1280 ◽  
Author(s):  
Jianan Pang ◽  
Qiaofa Shi ◽  
Zhiqiang Liu ◽  
Jin He ◽  
Huan Liu ◽  
...  
2006 ◽  
Vol 290 (5) ◽  
pp. R1357-R1365 ◽  
Author(s):  
Denis A. Evseenko ◽  
James W. Paxton ◽  
Jeffrey A. Keelan

ATP-binding cassette (ABC) efflux transporters are expressed in the human placenta where they are thought to help protect the fetus from xenobiotics. To evaluate models for analysis of ABC transporter function and regulation in the placenta, we have characterized the expression and activity of multidrug resistance (MDR) 1/P glycoprotein (Pgp), MDR3/Pgp, breast cancer resistance protein (BCRP), and multidrug resistance proteins 1 and 2 (MRPs 1, 2) in differentiating primary trophoblast cells and BeWo and Jar cell lines. Real-time PCR and immunoblotting were used for analysis of mRNA and protein expression, respectively. Functional activity was measured using selective inhibitors of efflux of fluorescent substrates, calcein-AM (Pgp and MRPs) and Hoechst 33342 (BCRP). The levels of MDR1 mRNA and protein expression were much higher in trophoblast than in Jar and especially BeWo cells. Expression of MDR3 protein was also lower in BeWo cells. Levels of MDR3 expression were markedly higher than MDR1 levels in all tested cell types. Levels of both MDR1 and MDR3 expression decreased during trophoblast differentiation/syncytialization. BCRP was highly expressed in all cell types and increased with trophoblast differentiation. MRP1 expression was much lower in trophoblasts compared with both cell lines. In contrast to its abundant mRNA expression, MRP2 protein was practically undetectable in BeWo and Jar cells and was present only at very low levels in trophoblast. Functional studies confirmed the presence of active Pgp and BCRP in all studied cell types, whereas MRP functional activity was detected only in BeWo and Jar cells. Both cell lines may be useful models for studying various aspects of placental ABC transporter expression and function, but also have significant limitations. With respect to their ABC protein expression profile, Jar cells are more similar to nondifferentiated cytotrophoblast, whereas BeWo appear to more closely reflect differentiated syncytiotrophoblast.


2017 ◽  
Vol 77 (04) ◽  
pp. 379-395
Author(s):  
L Schmieding ◽  
A Klein ◽  
N Maass ◽  
C Eckmann-Scholz ◽  
D Lütjohann ◽  
...  

2015 ◽  
Vol 16 (12) ◽  
pp. 1356-1371 ◽  
Author(s):  
Haigang Cui ◽  
Anna Zhang ◽  
Mingwei Chen ◽  
Johnson Liu

Toxicology ◽  
2013 ◽  
Vol 310 ◽  
pp. 29-38 ◽  
Author(s):  
Farah Koraïchi ◽  
Lilia Inoubli ◽  
Nadjem Lakhdari ◽  
Léo Meunier ◽  
Aurélie Vega ◽  
...  

2021 ◽  
Author(s):  
Moataz Dowaidar

Cancer cell multidrug resistance (MDR) is one of the most significant barriers to chemotherapy patients' ability to treat malignant tumors.This review first discusses the basic processes of MDR and then details the newest usage of nanomaterials combining multiple therapeutic approaches (e.g. PDT, PTT, gas therapy, gene therapy, and CDT) with MDR chemotherapy. We also analyze the advantages and rationales of these combination systems and why they can reduce MDR cancer cells. Currently, together with various new treatment approaches, MDR-related chemotherapeutic research is gaining momentum in search of better therapeutic results. PDT, for example, has the ability to eliminate high-efficiency multidrug-resistant malignancies but has limited relevance to tumor treatment. In this perspective, SDT is a highly promising approach as it increases ROS production utilizing ultrasonic vibrations, allowing magnitude orders to reach deeper than light. PTT is also often criticized for NIR light's restricted penetration depth; thermomagnetic therapy, using magnetic fields to produce local tissue hyperthermia, can considerably alleviate this problem. However, current research on the possibilities of using these new technologies to fight MDR remains rather rare, and more combination strategies should be carefully investigated in the future. Moreover, ongoing discoveries of cell death pathways, highlighted by recent ferroptosis findings, present a new strategy for our battle against MDR and may revolutionize our knowledge of MDR formation. Ferroptotic cell death promises to treat MDR in various cancers. While most of this cutting-edge research is still in its infancy, we anticipate gaining a deeper understanding of the effectiveness of these revolutionary anti-MDR medicines in the near future.


2015 ◽  
Vol 6 (11) ◽  
pp. 1079-1086 ◽  
Author(s):  
K. Trumpi ◽  
B.L. Emmink ◽  
A.M. Prins ◽  
M.G.H. van Oijen ◽  
P.J. van Diest ◽  
...  

1998 ◽  
Vol 16 (11) ◽  
pp. 3674-3690 ◽  
Author(s):  
D M Bradshaw ◽  
R J Arceci

For cytotoxic agents to have an effect on tumor cells, drugs must first be transported into the cell, potentially be metabolized to an active form, and interact appropriately with target molecules. A final common pathway of cytotoxic agents is usually the initiation of programmed cell death, or apoptosis. Tumor cells overcome the effects of cytotoxic agents at one or more of these levels. The classic multidrug-resistance (MDR) phenotype, as mediated by the drug efflux pump, P-glycoprotein, is one of the most extensively studied mechanisms of drug resistance. Additional drug transporters, such as the multidrug resistance-associated proteins (MRPs), have also been identified and can convey drug-resistance phenotypes. Important questions remain as to how and whether such transport systems can be specifically measured and effectively targeted to improve therapeutic outcomes. Furthermore, alterations in drug targets, drug metabolism, repair of DNA damage caused by drugs, and the inability to initiate programmed cell death can all contribute to drug resistance and must be ultimately considered in the explanation of tumor-cell resistance to therapy. Continued exploration of the pharmacologic methods to circumvent drug resistance, as well as strategies that involve targeted therapy and immunomodulation, should increase the specificity and efficacy of treatments for patients with cancer.


2015 ◽  
Vol 35 (2) ◽  
pp. 1170-1178 ◽  
Author(s):  
YUNHUI HU ◽  
KAIYONG LI ◽  
MUHAMMAD ASADUZZAMAN ◽  
RAQUEL CUELLA ◽  
HUI SHI ◽  
...  

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