ArticleCancer science2012
PDE5 inhibitors, sildenafil and vardenafil, reverse multidrug resistance by inhibiting the efflux function of multidrug resistance protein 7 (ATP-binding Cassette C10) transporter.
Article in Cancer science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Membrane-Mediated Action of Phosphodiesterase 5 Inhibitors.Pharmaceutics · 2025Article
- Recent developments on microwave-assisted organic synthesis of nitrogen- and oxygen-containing preferred heterocyclic scaffolds.RSC advances · 2023Review
- How do phosphodiesterase-5 inhibitors affect cancer? A focus on glioblastoma multiforme.Pharmacological reports : PR · 2022Review
- The Potential Role of Sildenafil in Cancer Management through EPR Augmentation.Journal of personalized medicine · 2021Review
- Article
- MY-5445, a phosphodiesterase type 5 inhibitor, resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to cytotoxic anticancer drugs.American journal of cancer research · 2020Article
- Drug repurposing to overcome resistance to various therapies for colorectal cancer.Cellular and molecular life sciences : CMLS · 2019Review
- Chk1 Inhibitor MK-8776 Restores the Sensitivity of Chemotherapeutics in P-glycoprotein Overexpressing Cancer Cells.International journal of molecular sciences · 2019Article
- Fragment-centric topographic mapping method guides the understanding of ABCG2-inhibitor interactions.RSC advances · 2019Article
- Repurposing drugs in oncology (ReDO)-selective PDE5 inhibitors as anti-cancer agents.Ecancermedicalscience · 2018Article
- Inhibition of PDE5A1 guanosine cyclic monophosphate (cGMP) hydrolysing activity by sildenafil analogues that inhibit cellular cGMP efflux.The Journal of pharmacy and pharmacology · 2017Article
- Article
- Potential synergistic effect of phosphodiesterase inhibitors with chemotherapy in lung cancer.Journal of Cancer · 2017Article
- Multidrug Resistance Proteins (MRPs) and Cancer Therapy.The AAPS journal · 2015Review
- FL118, a novel camptothecin analogue, overcomes irinotecan and topotecan resistance in human tumor xenograft models.American journal of translational research · 2015Article
- Sildenafil inhibits the growth of human colorectal cancer in vitro and in vivo.American journal of cancer research · 2015Article
- Co-delivery of Sildenafil (Viagra(®)) and Crizotinib for synergistic and improved anti-tumoral therapy.Pharmaceutical research · 2014Article
- PDE5 inhibitors enhance the lethality of standard of care chemotherapy in pediatric CNS tumor cells.Cancer biology & therapy · 2014Article
- Recent advances regarding the role of ABC subfamily C member 10 (ABCC10) in the efflux of antitumor drugs.Chinese journal of cancer · 2014Review
- Phosphodiesterase 5 inhibitors enhance chemotherapy killing in gastrointestinal/genitourinary cancer cells.Molecular pharmacology · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Phosphodiesterase type 5 (PDE5) inhibitors are widely used in the treatment of male erectile dysfunction and pulmonary hypertension. Recently, several groups have evaluated the ability of PDE5 inhibitors for their anticancer activities. Previously, we had shown that sildenafil, vardenafil and tadalafil could reverse P-glycoprotein (ATP-binding cassette B1)-mediated MDR. In the present study, we determined whether these PDE5 inhibitors have the potential to reverse multidrug resistance protein 7 (MRP7; ATP-binding cassette C10)-mediated MDR. We found that sildenafil and vardenafil dose-dependently enhanced the sensitivity of MRP7-transfected HEK293 cells to paclitaxel, docetaxel and vinblastine, while tadalafil had only a minimal effect. Accumulation and efflux experiments demonstrated that sildenafil and vardenafil increased the intracellular accumulation of [(3)H]-paclitaxel by inhibiting the efflux of [(3 H]-paclitaxel in HEK/MRP7 cells. In addition, immunoblot and immunofluorescence analyses indicated that no significant alterations of MRP7 protein expression and localization in plasma membranes were found after treatment with sildenafil, vardenafil or tadalafil. These results demonstrate that sildenafil and vardenafil reverse MRP7-mediated a MDR through inhibition of the drug efflux function of MRP7. Our findings indicate a potentially novel use of PDE5 inhibitors as an adjuvant chemotherapeutic agent in clinical practice.
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