PDE5 inhibitors, sildenafil and vardenafil, reverse multidrug resistance by inhibiting the efflux function of multidrug resistance protein 7 (ATP-binding Cassette C10) transporter.

Cancer Science
Jun-Jiang ChenZhe-Sheng Chen

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 rever...Continue Reading

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Citations

Mar 14, 2014·Pharmaceutical Research·João G MarquesIlídio J Correia
Oct 10, 2013·Chinese Journal of Cancer·Rishil J KathawalaZhe-Sheng Chen
Apr 5, 2015·The AAPS Journal·Yun-Kai ZhangZhe-Sheng Chen
Jan 3, 2015·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Rishil J KathawalaZhe-Sheng Chen
Jul 15, 2016·American Journal of Physiology. Renal Physiology·Kunyu ShenGlenda C Gobe
Apr 16, 2018·Archiv der Pharmazie·Lina Y El-SharkawyAshraf H Abadi
May 16, 2019·Cellular and Molecular Life Sciences : CMLS·Winnie Fong, Kenneth K W To
Aug 25, 2019·International Journal of Molecular Sciences·Qingbin CuiZhe-Sheng Chen
Jul 3, 2021·Journal of Personalized Medicine·Mohamed HaiderKhaled Greish

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