ArticlePharmaceutical research2011
siRNA-mediated down-regulation of P-glycoprotein in a Xenograft tumor model in NOD-SCID mice.
Article in Pharmaceutical research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed, 25 citations in OpenAlex.
- Aptamer-functionalized Hybrid Nanoparticles to Enhance the Delivery of Doxorubicin into Breast Cancer Cells by Silencing P-glycoprotein.Journal of cancer treatment & diagnosis · 2020Article
- Phospholipid-modified PEI-based nanocarriers for in vivo siRNA therapeutics against multidrug-resistant tumors.Gene therapy · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe efficacy of chemotherapy is decreased due to over-expression of the drug transporter P-glycoprotein (P-gp). This study was conducted to determine the feasibility of down-regulating tumor P-gp levels with non-viral siRNA delivery in order to sensitize the tumors to drug therapy.
methodsP-gp over-expressing MDA435/LCC6 MDR1 cells were used to establish xenografts in NOD-SCID mouse. Cationic polymers polyethylenimine (PEI) and stearic acid-substituted poly-L-lysine (PLL-StA) were formulated with P-gp- specific siRNAs and delivered intratumorally to explore the feasibility of P-gp down-regulation in tumors. Intravenous Doxil™ was administered to investigate tumor growth.
resultsPEI and PLL-StA effectively delivered siRNA to MDA435/LCC6 MDR1 cells in vitro to reduce P-gp expression for 3 days. Intratumoral injection of siRNA with the carriers resulted in 60-80% and 20-32% of siRNA retention in tumors after 24 and 96 hr, respectively. This led to ~29.0% and ~61.5% P-gp down-regulation with PEI- and PLL-StA-mediated siRNA delivery, respectively. The P-gp down-regulation by intratumoral siRNA injection led to better response to systemic Doxil™ treatment, resulting in slowed tumor growth in originally doxorubicin-resistant tumors.
conclusionEffective P-gp down-regulation was feasible with polymeric siRNA delivery in a xenograft model, resulting in an enhanced response to the drug therapy.
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Registered trials
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