Abstract:
Introduction:
Ranked second most diagnosed cancer and the fifth leading cause of cancer-related deaths
among men, prostate cancer (PCa) constitutes a major medical health issue. Despite the fact that many
therapeutic approaches exist against PCa, most cases often develop into a more advanced and lethal
stage known as metastatic castration-resistant prostate cancer (mCRPC). Hence, unfolding new
therapeutics to treat and manage PCa is of crucial importance. Drug repurposing is a growing research
field based on using previously approved drugs with known pharmacokinetic and pharmacodynamic
characteristics, for indications other than their traditional ones, like cancer. Non-steroidal anti-
inflammatory drugs (NSAIDs) have been studied as anti-neoplastic agents in several malignancies.
Objective:
In this study, we are interested in assessing the anti-tumorigenic effects of the NSAID
Piroxicam (PXM), alone and in combination with conventional therapies, on two PCa cell lines in vitro.
Material and Methods:
PXM, alone and in combination with conventional therapies (docetaxel and enzalutamide), will be tested on two cell lines
established in our laboratory that have the same defined Pten‑/‑TP53‑/‑ background representing two
different stages of PCa disease: PLum-AD (androgen-dependent) and PLum-AI (androgen-
independent). MTT assay will be performed to screen the cytotoxic effect of a wide battery of PXM
concentrations on those two cell lines. Then, trypan blue exclusion assay will be done to study PXM’s
effect on cell viability. Afterwards, wound healing will be used to study the ability of PXM in inhibiting
cell migration. Furthermore, 3D-sphere formation assay will be performed to assess the effect of PXM
in targeting PCa progenitor/stem cells.
Results/anticipated results:
MTT preliminary results showed that PXM has a dose-dependent cytotoxic effect and a synergistic effect with both conventional drugs on PCa cells.
Similar effects are obtained using trypan blue exclusion method. In addition, PXM inhibits and synergistically increases the effect of docetaxel and enzalutamide on migratory index of PCa cells and the sphere-forming abilities of cells.
Conclusion:
NSAIDs represent a potential candidate to be repurposed against PCa. We expect PXM, an
FDA-approved drug, to show anti-cancer effects against PCa cells including progenitor cells, and to
enhance the effect of already existing PCa treatments, overcoming resistance obstacles limiting
conventional treatments leading to a more efficient management of the disease.