The results of recent studies allow the suggestion that the new analogs of calcitriol could be applied in an antitumor therapy, especially in combination with cytostatics. In this paper, the effect of (24R)-1,24-dihydroxyvitamin D₃ (PRI-2191) on antitumor activity in vivo of 5-fluorouracil (5-FU) has been evaluated. The experiments were performed in a human HT-29 colon cancer model. Mice bearing subcutaneous colon cancer tumors or tumors implanted orthotopically were treated with PRI-2191 and 5-FU in various schedules. 5-FU was administered to mice repeatedly at dose 75 mg/kg/day i.v. whereas vitamin D analog PRI-2191 was administered s.c. at dose 0,2 or 1 μg/kg/day five or three times per week, respectively. In all experiments it was shown that the analog PRI-2191 improved therapeutic effect of 5-FU but the best effect was observed after administration of PRI-2191 three times per week. Statistically significant inhibition of tumor growth in the combined therapy was observed. What is more, the interaction between both compounds could be showed as synergy.

The analysis of cell cycle and apoptosis in the cells derived from HT-29 subcutaneously implanted tumors showed significant increase in cells number at G1/G0 stage and decrease at cells number at S and G2M stage. Additionally, the tendency to decrease apoptosis in tumor cells from mice treated with PRI-2191 and 5-FU simultaneously was indicated. The general conclusion of this work is that analog PRI-2191 increased antitumor effect of 5-FU in the human colon cancer therapy and it seems that it could be useful for clinical applications.

REFERENCES: 

[1] Wietrzyk J., Milczarek M., Kutner A., Chodyński M., Pol. Pat. P-388252, 2009;

[2] Wietrzyk J., Pełczyńska M., Dzimira S., Kuśmierczyk H., Kutner A., Szelejewski W., Opolski A.: Steroids, 69 (10): 629-35, 2004;

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