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Anticancer Res. 2019 Feb;39(2):727-734. doi: 10.21873/anticanres.13169.

Simvastatin Strongly Augments Proapoptotic, Anti-inflammatory and Cytotoxic Activity of Oxicam Derivatives in Doxorubicin-resistant Colon Cancer Cells.

Author information

1
Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland kamila.sroda-pomianek@umed.wroc.pl.
2
Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland.
3
Department of Chemistry of Drugs, Wroclaw Medical University, Wroclaw, Poland.

Abstract

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.

KEYWORDS:

Oxicam derivatives; apoptosis; cancer combination therapy; cyclo-oxygenase-2; simvastatin

PMID:
30711951
DOI:
10.21873/anticanres.13169
[Indexed for MEDLINE]

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