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Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth

The Prostate Nov 07, 2019

Carbonetti G, Converso C, Clement T, et al. - PC3, DU-145, and 22Rv1 PCa cells were incubated with FABP5 inhibitors Stony Brook fatty acid-binding protein inhibitor 102 (SBFI-102) or SBFI-103 in the presence or absence of docetaxel or cabazitaxel, and cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay in order to evaluate whether FABP5 inhibitors synergized with semi-synthetic taxanes to provoke cytotoxicity in vitro and attenuate tumor growth in vivo. In the PCa cells, SBFI-102 and SBFI-103 produced cytotoxicity. Synergistic cytotoxic impacts in vitro were exhibited by the coincubation of the PCa cells with FABP5 inhibitors and docetaxel or cabazitaxel. Tumor growth was decreased by treatment of mice with FABP5 inhibitors and compared with treatment with each drug alone, a combination of FABP5 inhibitors with a submaximal dose of docetaxel diminished tumor growth to a greater extent. Hence, in PCa cells, FABP5 inhibitors raise the cytotoxic and tumor-suppressive impacts of taxanes. Moreover, the ability of these drugs to synergize could allow more efficient antitumor activity while permitting for dosages of docetaxel or cabazitaxel to be lowered, possibly reducing taxane-resistance.
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