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Marzena Pełczyńska 1Joanna Wietrzyk Janusz Madej 2Stanisław Dzimira 2Andrzej Kutner 3Adam Opolski 4

1. Polish Academy of Sciences, Institute of Immunology and Experimental Therapy (IITD), Rudolfa Weigla 12, Wrocław 53-114, Poland
2. Academy of Agriculture, Faculty of Veterinary Medicine, Norwida 31, Wrocław 50-375, Poland
3. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland
4. Jan Dlugosz Academy, Al. Armii Krajowej 13/15, Częstochowa 42-201, Poland


Much efforts have been made to obtain active and less toxic vitamin D analogs for new clinical applications. In the previous studies, we have demonstrated that 1,24-(OH)2D3 revealed a potent antiproliferative effect against various cancer cell lines in vitro and this effect was stronger than obtained with parental 1,25-(OH)2D3. Moreover, we have shown that this effect could be attributed to induction of cancer cell-differentiation. Our results indicate, that 1,24-(OH)2D3 exhibits lower calcemic activity as well as toxicity than calcitriol.

In the present study we have evaluated the antitumor effect of combined treatment with cisplatin or fluorouracil and vitamin D analog and analyzed the serum calcium level in tumor (WEHI-3) bearing mice.

Single therapy with cisplatin reduced tumor volume with tumor growth inhibition (TGI) of 74%. For 1,24-(OH)2D3 we obtained 45% TGI value. However, combined treatment led only to subadditive effect. For fluorouracil we obtained 67% TGI value and for combined treatment 91% - what meant synergistic effect between cytostatic and vitamin D analog. Combined treatment did not cause an increase in life-span in comparison to applying either agent alone. The toxicity of combined treatment was the same as a singular drug treatment.

In conclusion, combined treatment of cisplatin and 1,24-(OH)2D3 lead to subadditive effect and fluorouracil with this vitamin D derivative lead to synergistic effect in reducing tumor volume.


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Related papers

Presentation: Poster at V Multidyscyplinarna Konferencja Nauki o Leku, by Marzena Pełczyńska
See On-line Journal of V Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2006-01-31 09:31
Revised:   2009-06-07 00:44