Investigating the Antineoplastic Effect of NSAIDs (Piroxicam) and Statins (Atorvastatin) on Prostate Cancer: Novel Therapeutic Potential

Abstract

Prostate cancer (PCa) is currently a challenging medical health issue worldwide. For the last 30+ years, PCa has been the most common cancer among men. Mortality due to metastatic castration-resistant PCa (CRPC) becomes problematic due to a high number of patients developing resistance to therapy. Therefore, elucidating new therapeutics to treat PCa is a top research priority.

Non-steroidal anti-inflammatory drugs (NSAIDs) and lipid-lowering drugs (statins) have shown to have anti-tumorigenic effects in many cancers. Consequently, we were interested in testing the anti-cancer properties of NSAIDs (Piroxicam-PXM) and statins (Atorvastatin-Ato), alone or in combination, on novel murine PCa cells (PLum-AD and PLum-AI). We employed in vitro assays to assess the effect of those drugs at a functional cellular level. We started by testing for cell proliferation and viability using MTT cell growth assay and trypan blue exclusion assay, respectively. Significant reduction of growth of cells and viability were observed exhibiting the sensitivity of PLum-AD and PLum-AI cells to those drugs, in a dose and time-dependent manner. Additionally, we have demonstrated, by using wound healing assay, that PXM and Ato inhibit cell migration, an important feature in malignancy. Treated cells failed to migrate and close up the wound compared to untreated cells. Furthermore, we assessed the potential of PXM and Ato in targeting cancer stem/progenitor cells. Using the sphere-formation assay, the number and size of spheres formed was reduced significantly when PLum-AD and PLum-AI cells were treated with PXM and Ato, suppressing their sphere-formation capacity.

In summary, our study illuminated the potential use of PXM and Ato in inhibiting cell proliferation, viability, migration, and stemness of PLum-AD and PLum-AI cell lines, promising a potential novel management of the disease.