PO-465 Effect of pain management drugs in metastatic prostate cancer: in vitro studies

Abstract

IntroductionMetastatic castration-resistant prostate cancer (mCRPC) presents no curative treatment, being the median life expectancy of this patients about 14–20 months. Docetaxel (Doc) remains the current first line treatment of mCRPC, increasing the median overall survival by 13.6 months. During this time, the major impairing life-altering quality complication is cancer-induced pain. Local anaesthetics (LA) as morphine (Mor), lidocaine (Lid), ropivacaine (Rop) and levobupivacaine (Lev) are used to minimise pain. Several studies report the antiproliferative, cytotoxic and sensitisation to chemotherapy effects of LA in a variety of other cancers this project aims to study the effect of pain management drugs combined with docetaxel for treatment of mCRPC.Material and methodsCytotoxic effects of LA and Doc in monotherapy were evaluated in one cell line of mCRPC (PC3) by incubating the cells with various concentrations of Mor (175.2 and 350.5 nM), Lid 2% (426.7 and 853.4 nM), Rop (36.4, 72.9, 136.7 and 273.3 nM), Lev (43.3, 86.7 and 173.4 nM) and Doc (0.01–500 nM) during 48 and 72 hours. Afterwards cell proliferation was determined using sulforhodamine B (SRB) assay. To study the effect of LA combined with Doc, cells were incubated with LA in the previous concentrations for 72 hours, then a concentration of Doc that leads to 80% of maximal response (EC80) was added. After 48 and 72 hours SRB assay was performed.Results and discussionsResults indicate that, after 48 hour, there is a higher decrease in cell proliferation to 85.03%±2.75, 83.73%±2.17% and 85.43%±3.68, relatively to control, when higher concentrations of Lid, Rop and Lev were added, respectively. Results showed that the EC80 of Doc is 1.51 and 0.81 nM, for 48 and 72 hour respectively. Preliminary results of combined therapy demonstrate that the combination of Doc with the highest concentrations of Rop and Lev resulted in a significant decrease in cell proliferation to 57.22% and to 54.22%, respectively.ConclusionThese preliminary results suggest that Rop and Lev, the most potent LA, are the most effective drugs in sensitise PC3 cells to chemotherapy with docetaxel, potentiating the therapeutic effects.The authors would like to thank Foundation for Science and Technology (FCT) (Strategic Project CNC.IBILI UID/NEU/04539/2013) through partnership arrangement PT2020 – COMPETE 2020 – Operational Thematic Program for Competitiveness and Internationalisation (POCI) (POCI-01–0145-FEDER-007440) for financial support.