ArticleThe American journal of pathology2011
Increased expression of P-glycoprotein is associated with doxorubicin chemoresistance in the metastatic 4T1 breast cancer model.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 158 citations in OpenAlex.
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- Role of microRNA-4739 in enhancing cisplatin chemosensitivity by negative regulation of RHBDD2 in human cervical cancer cells.Cellular & molecular biology letters · 2024Article
- Mechanisms of Sorafenib Resistance in HCC Culture Relate to the Impaired Membrane Expression of Organic Cation Transporter 1 (OCT1).Journal of hepatocellular carcinoma · 2024Article
- Enhancing Paclitaxel Efficacy with Piperine-Paclitaxel Albumin Nanoparticles in Multidrug-Resistant Triple-Negative Breast Cancer by Inhibiting P-Glycoprotein.Pharmaceutics · 2023Article
- In Vivo Investigation of Supportive Immunotherapeutic Combination of Bifidobacterium infantis 35624 and Doxorubicin in Murine Breast Cancer.Probiotics and antimicrobial proteins · 2023Article
- Therapeutic Effects of Plant Extracts ofPlants (Basel, Switzerland) · 2023Article
- Overexpression of ABCB1 confers resistance to FLT3 inhibitor FN-1501 in cancer cells: in vitro and in vivo characterization.American journal of cancer research · 2023Article
- Inhibitory effects of postbiotic consisting sonication-killedIranian journal of microbiology · 2022Article
- Glycolipid-peptide conjugate vaccines elicit CD8Clinical & translational immunology · 2022Article
- Iron Promotes Cardiac Doxorubicin Retention and Toxicity Through Downregulation of the Mitochondrial Exporter ABCB8.Frontiers in pharmacology · 2022Article
- Acquired Drug Resistance Enhances Imidazoquinoline Efflux by P-Glycoprotein.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Anticancer potential of (-)-epicatechin in a triple-negative mammary gland model.The Journal of pharmacy and pharmacology · 2021Article
- piR-39980 mediates doxorubicin resistance in fibrosarcoma by regulating drug accumulation and DNA repair.Communications biology · 2021Article
- The Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells.Cancers · 2021Article
- Iron oxide nanoparticle targeted chemo-immunotherapy for triple negative breast cancer.Materials today (Kidlington, England) · 2021Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Development of drug resistance is one of the major causes of breast cancer treatment failure. The goal of this study was to understand the chemoresistance mechanism using the highly metastatic 4T1 breast cancer model, which emulates stage IV breast cancer in humans. The metastatic 4T1 breast cancer cell line treated with either doxorubicin or 5-FU showed a concentration-dependent reduced cell proliferation, with induced G2-phase growth arrest (doxorubicin) or G1-phase growth arrest (5-FU). Doxorubicin treatment partially suppressed the multiorgan metastasis of 4T1 breast cancer cells in the lung, heart, liver, and bone, compared with either 5-FU or cyclophosphamide. We isolated and characterized 4T1 breast cancer cells from doxorubicin-resistant metastatic tumors (cell line 4T1-R). Multiorgan metastasis of drug-resistant 4T1 breast tumors was totally resistant to doxorubicin treatment. Our results indicate that doxorubicin is localized exclusively in the cytoplasm of resistant 4T1 breast cancer cells and that it cannot reach the nucleus because of increased nuclear expression of P-glycoprotein. Pretreatment of doxorubicin-resistant 4T1-R breast cancer cells with verapamil, a general inhibitor of P-glycoprotein, increased nuclear translocation of doxorubicin and cellular cytotoxicity. Thus, impaired nuclear translocation of doxorubicin due to increased expression of P-glycoprotein is associated with doxorubicin resistance of highly metastatic 4T1 breast cancer.
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