ArticleCancer biology & therapy2015
Dasatinib reverses the multidrug resistance of breast cancer MCF-7 cells to doxorubicin by downregulating P-gp expression via inhibiting the activation of ERK signaling pathway.
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 89 citations in OpenAlex.
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- Glutathione-Sensitive Photosensitizer-Drug Conjugates Target the Mitochondria to Overcome Multi-Drug Resistance in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Inhibition of Autophagy and the Cytoprotective Role of Smac Mimetic against ROS-Induced Cancer: A Potential Therapeutic Strategy in Relapse and Chemoresistance Cases in Breast Cancer.Current issues in molecular biology · 2023Article
- Development of Polymersomes Co-Delivering Doxorubicin and Melittin to Overcome Multidrug Resistance.Molecules (Basel, Switzerland) · 2023Article
- A pH-responsive complex based on supramolecular organic framework for drug-resistant breast cancer therapy.Drug delivery · 2022Article
- Molecular design, synthesis and biological evaluation of novel 1,2,5-trisubstituted benzimidazole derivatives as cytotoxic agents endowed with ABCB1 inhibitory action to overcome multidrug resistance in cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- A pH-responsive complex based on supramolecular organic framework for drug-resistant breast cancer therapy.Drug delivery · 2022Article
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- Preclinical studies of the triazolo[1,5-Acta pharmaceutica Sinica. B · 2022Article
- Ketone-selenoesters as potential anticancer and multidrug resistance modulation agents in 2D and 3D ovarian and breast cancer in vitro models.Scientific reports · 2022Article
- 2-Hydroxyestradiol Overcomes Mesenchymal Stem Cells-Mediated Platinum Chemoresistance in Ovarian Cancer Cells in an ERK-Independent Fashion.Molecules (Basel, Switzerland) · 2022Article
- Pharmacokinetic herb-drug interactions between Aidi injection and doxorubicin in rats with diethylnitrosamine-induced hepatocellular carcinoma.BMC pharmacology & toxicology · 2021Article
- Interleukin-32θ Triggers Cellular Senescence and Reduces Sensitivity to Doxorubicin-Mediated Cytotoxicity in MDA-MB-231 Cells.International journal of molecular sciences · 2021Article
- Cyclodextrin-Based Hybrid Polymeric Complex to Overcome Dual Drug Resistance Mechanisms for Cancer Therapy.Polymers · 2021Article
- The Establishment of Quantitatively Regulating Expression Cassette with sgRNA TargetingFrontiers in cell and developmental biology · 2021Article
- Reduction of breast tumor drug resistance by 2,3,5,4'-tetrahydroxystilbene for exhibition synergic chemotherapeutic effect.PloS one · 2021Article
- Involvement of P-gp on Reversing Multidrug Resistance Effects of 23-Hydroxybetulinic Acid on Chemotherapeutic Agents.Frontiers in pharmacology · 2021Article
- Tanshinone IIA Inhibits Osteosarcoma Growth through a Src Kinase-Dependent Mechanism.Evidence-based complementary and alternative medicine : eCAM · 2021Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug resistance (MDR) is one of the major obstacles to the efficiency of cancer chemotherapy, which often results from the overexpression of drug efflux transporters such as P-glycoprotein (P-gp). In the present study, we determined the effect of dasatinib which was approved for imatinib resistant chronic myelogenous leukemia (CML) and (Ph(+)) acute lymphoblastic leukemia (ALL) treatment on P-gp-mediated MDR. Our results showed that dasatinib significantly increased the sensitivity of P-gp-overexpressing MCF-7/Adr cells to doxorubicin in MTT assays; thus lead to an enhanced cytotoxicity of doxorubicin in MCF-7/Adr cells. Additionally, dasatinib increased the intracellular accumulation, inhibited the efflux of doxorubicin in MCF-7/Adr cells, and significantly enhanced doxorubicin-induced apoptosis in MCF-7/Adr cells. Further studies showed that dasatinib altered the expression levels of mRNA, protein levels of P-gp, and the phosphorylation of signal-regulated kinase (ERK) both in time-dependent (before 24 h) and dose-dependent manners at concentrations that produced MDR reversals. In conclusion, dasatinib reverses P-gp-mediated MDR by downregulating P-gp expression, which may be partly attributed to the inhibition of ERK pathway. Dasatinib may play an important role in circumventing MDR when combined with other conventional antineoplastic drugs.
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