Cancers, Vol. 11, Pages 77: Fenofibrate Augments the Sensitivity of Drug-Resistant Prostate Cancer Cells to Docetaxel

Cancers, Vol. 11, Pages 77: Fenofibrate Augments the Sensitivity of Drug-Resistant Prostate Cancer Cells to Docetaxel Cancers doi: 10.3390/cancers11010077 Authors: Marcin Luty Katarzyna Piwowarczyk Anna Łabędź-Masłowska Tomasz Wróbel Małgorzata Szczygieł Jessica Catapano Grażyna Drabik Damian Ryszawy Sylwia Kędracka-Krok Zbigniew Madeja Maciej Siedlar Martyna Elas Jarosław Czyż Metronomic agents reduce the effective doses and adverse effects of cytostatics in cancer chemotherapy. Therefore, they can enhance the treatment efficiency of drug-resistant cancers. Cytostatic and anti-angiogenic effects of fenofibrate (FF) suggest that it can be used for the metronomic chemotherapy of drug-resistant prostate tumors. To estimate the effect of FF on the drug-resistance of prostate cancer cells, we compared the reactions of naïve and drug-resistant cells to the combined treatment with docetaxel (DCX)/mitoxantrone (MTX) and FF. FF sensitized drug-resistant DU145 and PC3 cells to DCX and MTX, as illustrated by their reduced viability and invasive potential observed in the presence of DCX/MTX and FF. The synergy of the cytostatic activities of both agents was accompanied by the inactivation of P-gp-dependent efflux, dysfunction of the microtubular system, and induction of polyploidy in DCX-resistant cells. Chemical inhibition of PPARα- and reactive oxygen species (ROS)-dependent pathways by GW6471 and N-acetyl-L-cystein...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research