ArticleCancer gene therapy2013
Polymeric delivery of siRNA for dual silencing of Mcl-1 and P-glycoprotein and apoptosis induction in drug-resistant breast cancer cells.
Article in Cancer gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed, 43 citations in OpenAlex.
- Small interfering RNA (siRNA)-based targeting breast cancer therapy.Discover oncology · 2026Review
- siRNA and targeted delivery systems in breast cancer therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Understanding MCL1: from cellular function and regulation to pharmacological inhibition.The FEBS journal · 2022Review
- Myeloid cell leukemia-1 is an important predictor of survival and progression of small cell lung cancer.Annals of translational medicine · 2020Article
- Prospects for RNAi Therapy of COVID-19.Frontiers in bioengineering and biotechnology · 2020Review
- Identification of Potential Drug Targets in Cancer Signaling Pathways using Stochastic Logical Models.Scientific reports · 2016Article
- Effect of siRNA pre-Exposure on Subsequent Response to siRNA Therapy.Pharmaceutical research · 2015Article
- Targeting Cell Cycle Proteins in Breast Cancer Cells with siRNA by Using Lipid-Substituted Polyethylenimines.Frontiers in bioengineering and biotechnology · 2015Article
- Expression of P-gp in acute myeloid leukemia and the reversal function of AsOncology letters · 2015Article
- Maritoclax induces apoptosis in acute myeloid leukemia cells with elevated Mcl-1 expression.Cancer biology & therapy · 2014Article
- Liposomal co-delivery of omacetaxine mepesuccinate and doxorubicin for synergistic potentiation of antitumor activity.Pharmaceutical research · 2014Article
- Sequence-dependent combination therapy with doxorubicin and a survivin-specific small interfering RNA nanodrug demonstrates efficacy in models of adenocarcinoma.International journal of cancer · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enhanced survival mechanisms of malignant cells in combination with elevated levels of drug transporters can sustain an undesirable resistance against drug therapy. Short interfering RNA (siRNA) delivery against targets involved in aberrant mechanisms is a promising approach and we hypothesize that simultaneous silencing of multiple targets could prove more advantageous than common approach to silence individual targets. To explore this approach, we targeted anti-apoptotic proteins myeloid cell leukemia 1 (Mcl-1) and survivin along with the efflux pump P-glycoprotein (P-gp) in drug-resistant breast cancer cells. Polymeric siRNA delivery was employed for this purpose by using small polyethylenimine (PEI) substituted with lipids. While silencing Mcl-1 caused ∼90% cell death in wild-type cells, this effect was less significant in P-gp over-expressing cells. An additive effect for Mcl-1 and P-gp silencing was evident in the latter cells, where simultaneous silencing of these targets created a significantly higher effect compared with silencing each individual target. Prolonged exposure of wild-type cells to doxorubicin (DOX) resulted in upregulation of P-gp, breast cancer resistance protein, survivin and Mcl-1. Dual silencing of P-gp and Mcl-1 again resulted in an additive effect in resistance-induced cells, which displayed an increased dependency on Mcl-1 for survival. Cytotoxic effect of DOX was also enhanced in resistance-induced cells after silencing Mcl-1. We conclude that polymer-mediated siRNA delivery can silence multiple targets simultaneously and reverse drug resistance.
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