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Int. J. Mol. Sci. 2015, 16(11), 27191-27207;

Vitamin D Analogs Potentiate the Antitumor Effect of Imatinib Mesylate in a Human A549 Lung Tumor Model

Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland
Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editors: Roman Perez-Fernandez and Efigenia Arias
Received: 25 September 2015 / Revised: 22 October 2015 / Accepted: 2 November 2015 / Published: 13 November 2015
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In previous papers, we presented data on studies on the anticancer activity of the vitamin D3 analogs, named PRI-2191 and PRI-2205, in different cancer models. In this study, we showed the improved antiproliferative activity of a combination of imatinib mesylate (Gleevec, GV) and cytostatic agents in in vitro studies, when used with a third compound, namely PRI-2191, in an A549 human lung cancer model. Furthermore, we analyzed the influence of both PRI-2191, as well as PRI-2205 on the anticancer activity of GV in mice bearing A549 tumors. The route of PRI-2191 analog administration showed a significant impact on the outcome of GV treatment: subcutaneous injection was more efficient and less toxic than oral gavage. Moreover, both vitamin D compounds increased the anticancer activity of GV; however, they might also potentiate some adverse effects. We also evaluated in tumor tissue the expression of VEGF, PDGF-BB, vitamin D receptor, CYP27B1, CYP24, p53 and Bcl-2, as well as PDGF receptors: α and β. We observed the upregulation of p53 expression and the downregulation of Bcl-2, as well as VEGF in A549 tumors as a result of the tested treatment. However, vitamin D analogs did not significantly influence the expression of these proteins. View Full-Text
Keywords: NSCLC; imatinib; vitamin D analogs NSCLC; imatinib; vitamin D analogs

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Maj, E.; Filip-Psurska, B.; Świtalska, M.; Kutner, A.; Wietrzyk, J. Vitamin D Analogs Potentiate the Antitumor Effect of Imatinib Mesylate in a Human A549 Lung Tumor Model. Int. J. Mol. Sci. 2015, 16, 27191-27207.

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