2. Academic Validation
  3. Vitamin D Analogs Potentiate the Antitumor Effect of Imatinib Mesylate in a Human A549 Lung Tumor Model

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

  • Int J Mol Sci. 2015 Nov 13;16(11):27191-207. doi: 10.3390/ijms161126016.
Ewa Maj 1,  Beata Filip-Psurska 2,  Marta Świtalska 3,  Andrzej Kutner 4,  Joanna Wietrzyk 5
Affiliations

Affiliations

  • 1 Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland. ewa.maj@iitd.pan.wroc.pl.
  • 2 Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland. fillip@iitd.pan.wroc.pl.
  • 3 Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland. switalska@iitd.pan.wroc.pl.
  • 4 Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland. a.kutner@ifarm.eu.
  • 5 Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland. wietrzyk@iitd.pan.wroc.pl.
PMID: 26580599 DOI: 10.3390/ijms161126016
Abstract

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.

Keywords

NSCLC; imatinib; vitamin D analogs.

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