ArticleNaunyn-Schmiedeberg's archives of pharmacology2016
In vitro and in vivo downregulation of the ATP binding cassette transporter B1 by the HMG-CoA reductase inhibitor simvastatin.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Bis-(di-4-phenyl-benzylaminethiocarbonyl)disulfide sensitizes ABCC2/ALDH3A1 overexpressing NSCLC cells to cisplatin.Cancer biology & therapy · 2026Article
- Enhanced antitumor activity of atorvastatin and luteolin, with or without doxorubicin, in a solid Ehrlich carcinoma mouse model: modulation of ABC transporters, telomerase, and cancer stem cells.Medical oncology (Northwood, London, England) · 2026Article
- Therapeutic Potential of Simvastatin: Cellular Mechanism, Binding Energetics, and Resistance Developments.Current topics in medicinal chemistry · 2025Review
- Exposure to statins post localized prostate cancer diagnosis and risk of metastasis among men who did not receive curative prostate cancer treatment.Cancer reports (Hoboken, N.J.) · 2023Article
- Glycoconjugate journal special issue on: the glycobiology of Parkinson's disease.Glycoconjugate journal · 2022Review
- Simvastatin treatment varies the radiation response of human breast cells in 2D or 3D culture.Investigational new drugs · 2021Article
- Lipophilic vs. hydrophilic statins and psychiatric hospitalizations and emergency room visits in US Veterans with schizophrenia and bipolar disorder.Pteridines · 2021Article
- Statins in risk-reduction and treatment of cancer.World journal of clinical oncology · 2020Review
- Time-dependent simvastatin administration enhances doxorubicin toxicity in neuroblastoma.Toxicology reports · 2020Article
- Amino Acid Signature in Human Melanoma Cell Lines from Different Disease Stages.Scientific reports · 2018Article
- Marketed drugs used for the management of hypercholesterolemia as anticancer armament.OncoTargets and therapy · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Extrusion of chemotherapeutics by ATP-binding cassette (ABC) transporters like ABCB1 (P-glycoprotein) represents a crucial mechanism of multidrug resistance in cancer therapy. We have previously shown that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin directly inhibits ABCB1, alters the glycosylation of the transporter, and enhances the intracellular accumulation of doxorubicin with subsequent anti-cancer action. Here, we show that simvastatin reduces endogenous dolichol levels and ABCB1 in human neuroblastoma SH-SY5Y cells. Coapplication with dolichol prevents the downregulation of the ABCB1 transporter. Importantly, dolichol also attenuated simvastatin-induced apoptosis, unmasking involvement of unfolded protein response. Direct monitoring of the fluorescent fusion protein YFP-ABCB1 further confirms concentration-dependent reduction of ABCB1 in HEK293 cells by simvastatin. In simvastatin-treated murine xenografts, ABCB1 was also reduced in the liver and rhabdomyosarcoma but did not reach significance in neuroblastoma. Nevertheless, the in vivo anti-cancer effects of simvastatin are corroborated by increased apoptosis in tumor tissues. These findings provide experimental evidence for usage of simvastatin in novel chemotherapeutic regimens and link dolichol depletion to simvastatin-induced anti-cancer activity.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.