Comparison of NSAIDs activity in COX-2 expressing and non-expressing 2D and 3D pancreatic cancer cell cultures

Ugnė Čeponytė, Miglė Paškevičiū tė, Vilma Petrikaitė Department of Drug Chemistry, Faculty of Pharmacy, Lithuanian University of Health Sciences, Kaunas, Lithuania Purpose: In this study, we evaluated the anticancer activity of non-steroidal anti-inflammatory drugs (NSAIDs) in BxPC-3 and MIA PaCa-2 pancreatic cancer cell cultures. Methods: To test the effect of compounds on the viability of cells, the MTT assay was used. The activity of NSAIDs in 3D cell cultures was evaluated by measuring the size change of spheroids. The type of cell death was identified by cell staining with Hoechst 33342 and propidium iodide. To evaluate the effect on the colony-forming ability of cancer cells, the clonogenic assay was used. Results: Five out of seven tested NSAIDs reduced the viability of BxPC-3 and MIA PaCa-2 cancer cells. Fenamates were more active against cyclooxygenase-2 expressing BxPC-3 than cyclooxygenase-2 non-expressing MIA PaCa-2 cell line. Fenamates and coxibs exerted higher activity in monolayer cultured cells, whereas salicylates were more active in 3D cultures. Fenamates and coxibs induced dose-dependent apoptosis and necrosis. NSAIDs also inhibited the colony-forming ability of cancer cells. Meclofenamic acid, niflumic acid, and parecoxib possessed higher activity on BxPC-3, and celecoxib possessed higher activity on MIA PaCa-2 cell colony formation. Conclusion: Our results show that fenamates, coxibs, and salicylates possess anticancer activity on human pancreatic cancer BxPC-3 and MIA PaCa-2 cell cultures. Keywords: anticancer activity, viability, spheroid, apoptosis, clonogenic assa