ArticleBMC cancer2009
The influence of P-glycoprotein expression and its inhibitors on the distribution of doxorubicin in breast tumors.
Article in BMC cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 63 citations in OpenAlex.
- Plasma concentrations of doxorubicin and cyclophosphamide during anthracycline-based chemotherapy in a pregnant breast cancer patient: evaluation of gestational changes.Cancer chemotherapy and pharmacology · 2026Article
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- Structural View of Cryo-Electron Microscopy-Determined ATP-Binding Cassette Transporters in Human Multidrug Resistance.Biomolecules · 2024Review
- A Targeted Thorium-227 Conjugate Demonstrates Efficacy in Preclinical Models of Acquired Drug Resistance and Combination Potential with Chemotherapeutics and Antiangiogenic Therapies.Molecular cancer therapeutics · 2023Article
- Effect of natural flavonoids to reverse P-glycoprotein-related multidrug resistance in breast cancer cell cultures.American journal of cancer research · 2022Article
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- New NO- and H2S-releasing doxorubicins as targeted therapy against chemoresistance in castration-resistant prostate cancer: in vitro and in vivo evaluations.Investigational new drugs · 2018Article
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- Selective targeting and therapy of metastatic and multidrug resistant tumors using a long circulating podophyllotoxin nanoparticle.Biomaterials · 2017Article
- A Simple and Improved Active Loading Method to Efficiently Encapsulate Staurosporine into Lipid-Based Nanoparticles for Enhanced Therapy of Multidrug Resistant Cancer.Pharmaceutical research · 2016Article
- A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors.Biomaterials · 2015Article
- Carboxymethylcellulose-based and docetaxel-loaded nanoparticles circumvent P-glycoprotein-mediated multidrug resistance.Molecular pharmaceutics · 2014Article
- Development of a PET radiotracer for non-invasive imaging of the reactive oxygen species, superoxide, in vivo.Organic & biomolecular chemistry · 2014Article
- Effect of small-molecule modification on single-cell pharmacokinetics of PARP inhibitors.Molecular cancer therapeutics · 2014Article
- Effect of transcatheter intraarterial therapies on the distribution of Doxorubicin in liver cancer in a rabbit model.PloS one · 2013Article
- Evolutionary approaches to prolong progression-free survival in breast cancer.Cancer research · 2012Article
- The distribution and retention of paclitaxel and doxorubicin in multicellular layer cultures.Oncology reports · 2012Article
- The controversial role of ABC transporters in clinical oncology.Essays in biochemistry · 2011Review
- Bioengineering approaches to study multidrug resistance in tumor cells.Integrative biology : quantitative biosciences from nano to macro · 2011Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundAnti-cancer drugs access solid tumors via blood vessels, and must penetrate tumor tissue to reach all cancer cells. Previous studies have demonstrated steep gradients of decreasing doxorubicin fluorescence with increasing distance from blood vessels, such that many tumor cells are not exposed to drug. Studies using multilayered cell cultures show that increased P-glycoprotein (PgP) is associated with better penetration of doxorubicin, while PgP inhibitors decrease drug penetration in tumor tissue. Here we evaluate the effect of PgP expression on doxorubicin distribution in vivo.
methodsMice bearing tumor sublines with either high or low expression of PgP were treated with doxorubicin, with or without pre-treatment with the PgP inhibitors verapamil or PSC 833. The distribution of doxorubicin in relation to tumor blood vessels was quantified using immunofluorescence.
resultsOur results indicate greater uptake of doxorubicin by cells near blood vessels in wild type as compared to PgP-overexpressing tumors, and pre-treatment with verapamil or PSC 833 increased uptake in PgP-overexpressing tumors. However, there were steeper gradients of decreasing doxorubicin fluorescence in wild-type tumors compared to PgP overexpressing tumors, and treatment of PgP overexpressing tumors with PgP inhibitors led to steeper gradients and greater heterogeneity in the distribution of doxorubicin.
conclusionPgP inhibitors increase uptake of doxorubicin in cells close to blood vessels, have little effect on drug uptake into cells at intermediate distances, and might have a paradoxical effect to decrease doxorubicin uptake into distal cells. This effect probably contributes to the limited success of PgP inhibitors in clinical trials.
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