The effects of esomeprazole combined with classical cancer drugs on lung cancer cells and peripheral blood mononuclear cells
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1
Uludag University Faculty of Medicine, Department of Medical Biochemistry, Türkiye
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2
Uludag University Faculty of Medicine, Department of Immunology, Türkiye
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3
Uludag University Faculty of Medicine, Department of Biostatistics, Türkiye
Ascidity of tumour microenviroment is one of the important factors in resistance to chemotherapeutics. Proton pumps, referred as vacuolar H+ATPases (V-ATPases), play a critical role by transfering H+ ion from cell cytoplasm into extracellular compartment. In this study, to examine if esomeprazole, a proton pump inhibitor, increases the sensitivity of A-549 cells, a lung cancer cell line, to classical drugs used for lung cancer treatment, when it is applied in combination. For this aim, the combination of classical drugs used for lung cancer treatment (cisplatin, carboplatin, paciltaxel, docetaxel, gemcitabine and vinorelbine) with esomeprazole were applied onto A-549 cells, and then, their cytotoxic effects were evaluated with Methyl Thiazol Tetrazolium (MTT) Assay, ATP-TCA and M30 ELISA. It was demonstrated that combinations of esomeprazole only with cisplatin and carboplatin lead to significant increase in cytotoxicity. This increased cytotoxicity was not seen in combinations with other drugs. Additionally, M30 (an apoptotic marker) levels were measured in order to determine the cell death mechanism. The increase of M30 levels in carboplatin alone and in combination with esomeprazole exhibit that carboplatin causes cell death by apoptosis. However, the fact that no increase was observed with ciplatin alone and in combination with esomeprazole suggested that cisplatin, unlike carboplatin, leads to cell death by necrosis. Furthermore, the cytotoxic effect of esomeprazole alone and in combination with cancer drugs on lymphocytes were investigated with MTT and flow cytmetric cell cycle analysis. When compared with control group apoptotic cell ratio was dose-dependently increased with both esomeprazole alone and in combination with cisplatin or carboplatin. The data obtained in this study suggest that espomeprazole augments the sensitivity of tumour cells to chemotherapeutics, and also, may protect the host from side effects caused by the use of high doses of cancer drugs.
Keywords:
esomeprazole,
lung cancer,
Proton Pump Inhibitors,
A549,
Cisplatin
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
YILMAZTEPE ORAL
A,
KORKMAZ
Ş,
BUDAK
F,
ÖZKAYA
G,
ULUKAYA
E and
ORAL
HB
(2013). The effects of esomeprazole combined with classical cancer drugs on lung cancer cells and peripheral blood mononuclear cells.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00898
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Received:
24 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. ARZU YILMAZTEPE ORAL, Uludag University Faculty of Medicine, Department of Medical Biochemistry, BURSA, 16059, Türkiye, arzuy@uludag.edu.tr
Prof. HALUK B ORAL, Uludag University Faculty of Medicine, Department of Immunology, Bursa, Türkiye, oralb@uludag.edu.tr