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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
| Content Provider | Scilit |
|---|---|
| Author | Chen, Ting Wang, Changyuan Liu, Qi Meng, Qiang Sun, Huijun Huo, Xiaokui Sun, Pengyuan Peng, Jinyong Liu, Zhihao Yang, Xiaobo Liu, Kexin |
| Copyright Year | 2014 |
| Description | Journal: Cancer Biology & Therapy 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622436/pdf |
| Ending Page | 114 |
| Page Count | 9 |
| Starting Page | 106 |
| ISSN | 15384047 |
| e-ISSN | 15558576 |
| DOI | 10.4161/15384047.2014.987062 |
| Journal | Cancer Biology & Therapy |
| Issue Number | 1 |
| Volume Number | 16 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2014-11-20 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Biology & Therapy Biochemistry and Molecular Biology Erkextracellular Signal-regulated Kinase Multidrug Resistance Phosphorylated Extracellular Signal–regulated Kinase P-glycoprotein |
| Content Type | Text |
| Subject | Cancer Research Pharmacology Molecular Medicine Oncology |
