ArticlePharmaceutical research2015
Effect of siRNA pre-Exposure on Subsequent Response to siRNA Therapy.
Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
5 citing papers in PubMed, 13 citations in OpenAlex.
- Multidrug Resistance: Are We Still Afraid of the Big Bad Wolf.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Lipopolymers as the Basis of Non-Viral Delivery of Therapeutic siRNA Nanoparticles in a Leukemia (MOLM-13) Model.Biomolecules · 2025Article
- Article
- Heterogeneity and Plasticity of Human Breast Cancer Cells in Response to Molecularly-Targeted Drugs.Frontiers in oncology · 2019Article
- Advances in biology of acute lymphoblastic leukemia (ALL) and therapeutic implications.American journal of blood research · 2018Review
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 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAn alternative cancer therapy based on RNA interference (RNAi) has shown considerable promise but the possibility of resistance development is not known. This study explored the possibility of therapeutic resistance against siRNA nanoparticles in human cancer cells.
methodsTwo approaches to siRNA treatment were undertaken using lipid-modified polyethylenimines, a single high concentration (shock) and repeated increasing concentrations (gradual). The targets were Mcl-1, RPS6KA5 and KSP in MDA-MB-435 cells.
resultsThere was no evidence of resistance development in shock-treated cells, while the decrease in mRNA levels of targeted proteins was not as robust in naïve cells in gradual treatment. However, silencing efficiency was restored after a 7-day recovery period when expression of suppressed proteins returned to normal levels. Cellular uptake of siRNA was not affected by pre-treatments. Other mediators involved in cell survival and proliferation were altered in siRNA-treated cells, but only JUN silencing led to a heightened loss of viability. In vivo experiments demonstrated similar silencing efficiency at mRNA level after repeat doses.
conclusionsHuman cancer cells responded to repeat siRNA nanoparticles in a similar fashion after a temporary initial alteration and little, if any, resistance was evident against repeated siRNA treatments.
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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.