Inhibition of the Lysophosphatidylinositol Transporter ABCC1 Reduces Prostate Cancer Cell Growth and Sensitizes to Chemotherapy
Metabolic Signalling Group, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia
Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
Prostate Cancer Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, VI 3000, Australia
Cancer Program, Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Clayton, VI 3800, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VI 3010, Australia
Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy
Drug Discovery Research Center, USA Health Mitchell Cancer Institute, Mobile, AL 36604-1405, USA
Author to whom correspondence should be addressed.
Cancers 2020, 12(8), 2022; https://doi.org/10.3390/cancers12082022
Received: 6 May 2020 / Revised: 13 July 2020 / Accepted: 17 July 2020 / Published: 23 July 2020
(This article belongs to the Special Issue The Role of Drug Resistance-Associated Proteins in Cancer: from Conventional Anticancer Drugs to Targeting Drugs)
Expression of ATP-binding cassette (ABC) transporters has long been implicated in cancer chemotherapy resistance. Increased expression of the ABCC subfamily transporters has been reported in prostate cancer, especially in androgen-resistant cases. ABCC transporters are known to efflux drugs but, recently, we have demonstrated that they can also have a more direct role in cancer progression. The pharmacological potential of targeting ABCC1, however, remained to be assessed. In this study, we investigated whether the blockade of ABCC1 affects prostate cancer cell proliferation using both in vitro and in vivo models. Our data demonstrate that pharmacological inhibition of ABCC1 reduced prostate cancer cell growth in vitro and potentiated the effects of Docetaxel in vitro and in mouse models of prostate cancer in vivo. Collectively, these data identify ABCC1 as a novel and promising target in prostate cancer therapy.