PT - JOURNAL ARTICLE AU - KAMILA ŚRODA-POMIANEK AU - KRYSTYNA MICHALAK AU - ANNA PALKO-ŁABUZ AU - ANNA URYGA AU - BERENIKA SZCZĘŚNIAK-SIĘGA AU - OLGA WESOŁOWSKA TI - Simvastatin Strongly Augments Proapoptotic, Anti-inflammatory and Cytotoxic Activity of Oxicam Derivatives in Doxorubicin-resistant Colon Cancer Cells AID - 10.21873/anticanres.13169 DP - 2019 Feb 01 TA - Anticancer Research PG - 727--734 VI - 39 IP - 2 4099 - http://ar.iiarjournals.org/content/39/2/727.short 4100 - http://ar.iiarjournals.org/content/39/2/727.full SO - Anticancer Res2019 Feb 01; 39 AB - Background: Incidence of cancer is still increasing. Chemotherapy is often unsuccessful; moreover, anticancer drugs cause serious side-effects. It is necessary to develop effective agents for combination therapies that would increase antitumor effects of treatment and reduce its side-effects. Materials and Methods: Anticancer activity of oxicam derivatives (PR17 and PR18) alone and in combination with simvastatin on doxorubicin-resistant colon cancer cells was studied. Apoptosis was investigated via caspase-3 activation assay as well as via western blot analysis of expression of apoptotic components, B-cell lymphoma 2 protein (BCL2) and BCL2-associated X protein (BAX). Expression and activity of cyclo-oxygenase-2 (COX2) was also assessed. Results: Oxicam derivatives induced apoptosis through a caspase-3-dependent pathway, up-regulated BAX expression, and down-regulated BCL2 expression. Additionally, oxicam derivatives reduced expression and activity of COX2. Effect of oxicam derivatives on these processes was strongly potentiated by simvastatin. Conclusion: Oxicam derivatives at low concentrations effectively inhibit growth of cancer cells after co-administration with simvastatin.