ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
A double-modulation strategy in cancer treatment with a chemotherapeutic agent and siRNA.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Small non-coding RNAs: key regulatory factors and potential therapeutic targets in tumor immunity.Frontiers in immunology · 2025Review
- Improvement of 5-fluorouracil chemosensitivity in colorectal cancer cells by siRNA-mediated silencing of STAT6 oncogene.Iranian journal of basic medical sciences · 2024Article
- Multifunctional nanoparticles co-loaded with Adriamycin and MDR-targeting siRNAs for treatment of chemotherapy-resistant esophageal cancer.Journal of nanobiotechnology · 2022Article
- Delivery of mitochondriotropic doxorubicin derivatives using self-assembling hyaluronic acid nanocarriers in doxorubicin-resistant breast cancer.Acta pharmacologica Sinica · 2018Article
- siRNA Knockdown of RRM2 Effectively Suppressed Pancreatic Tumor Growth Alone or Synergistically with Doxorubicin.Molecular therapy. Nucleic acids · 2018Article
- Imaging of Nanoparticle Distribution to Assess Treatments That Alter Delivery.Molecular imaging and biology · 2018Review
- Evaluation of the potential of a simplified co-delivery system with oligodeoxynucleotides as a drug carrier for enhanced antitumor effect.International journal of nanomedicine · 2018Article
- Tackling breast cancer chemoresistance with nano-formulated siRNA.Gene therapy · 2016Review
- Novel polymer micelle mediated co-delivery of doxorubicin and P-glycoprotein siRNA for reversal of multidrug resistance and synergistic tumor therapy.Scientific reports · 2016Article
- Micelle-like nanoparticles as carriers for DNA and siRNA.Molecular pharmaceutics · 2015Review
- X-linked inhibitor of apoptosis-associated factor l (XAFl) enhances the sensitivity of colorectal cancer cells to cisplatin.Medical oncology (Northwood, London, England) · 2014Article
- Nanocarrier mediated delivery of siRNA/miRNA in combination with chemotherapeutic agents for cancer therapy: current progress and advances.Journal of controlled release : official journal of the Controlled Release Society · 2014Review
- siRNA nanoparticles: the future of RNAi therapeutics for oncology?Nanomedicine (London, England) · 2014Article
- The combined effects of irradiation and herpes simplex virus type 1 infection on an immortal gingival cell line.Virology journal · 2014Article
- Enhanced activity of doxorubicin in drug resistant A549 tumor cells by encapsulation of P-glycoprotein inhibitor in PLGA-based nanovectors.Oncology letters · 2014Article
- Effective inhibition of colon cancer cell growth with MgAl-layered double hydroxide (LDH) loaded 5-FU and PI3K/mTOR dual inhibitor BEZ-235 through apoptotic pathways.International journal of nanomedicine · 2014Article
- Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.Journal of controlled release : official journal of the Controlled Release Society · 2013Review
- The co-delivery of oxaliplatin abrogates the immunogenic response to PEGylated siRNA-lipoplex.Pharmaceutical research · 2013Article
- Bioengineering strategies for designing targeted cancer therapies.Advances in cancer research · 2013Review
- Co-delivery of siRNA and therapeutic agents using nanocarriers to overcome cancer resistance.Nano today · 2012Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Fluorouracil (5-FU) is broadly considered the drug of choice for treating human colorectal cancer (CRC). However, 5-FU resistance, mainly caused by the overexpression of antiapoptotic proteins such as Bcl-2, often leads ultimately to treatment failure. We here investigated the effect of Bcl-2 gene silencing, using small interfering RNA (siRNA) (siBcl-2), on the efficacy of 5-FU in CRC. Transfection of siBcl-2 by a Lipofectamine2000/siRNA lipoplex effectively downregulated Bcl-2 expression in the DLD-1 cell line (a CRC), resulting in significant cell growth inhibition in vitro upon treatment with 5-FU. For in vivo treatments, S-1, an oral formulation of Tegafur (TF), a prodrug of 5-FU, was used to mimic 5-FU infusion. The combined treatment of polyethylene glycol (PEG)-coated siBcl-2-lipoplex and S-1 showed superior tumor growth suppression in a DLD-1 xenograft model, compared to each single treatment. Surprisingly, daily S-1 treatment enhanced the accumulation of PEG-coated siBcl-2-lipoplex in tumor tissue. We propose a novel double modulation strategy in cancer treatment, in which chemotherapy enhances intratumoral siRNA delivery and the delivered siRNA enhances the chemosensitivity of tumors. Combination of siRNA-containing nanocarriers with chemotherapy may compensate for the limited delivery of siRNA to tumor tissue. In addition, such modulation strategy may be considered a promising therapeutic approach to successfully managing 5-FU-resistant tumors.
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