Vitamin D analogs enhance the anticancer activity of 5-fluorouracil in an in vivomouse colon cancer model
Open Access
- 18 June 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 13 (1), 294-19
- https://doi.org/10.1186/1471-2407-13-294
Abstract
Active vitamin D analogs that are less toxic than calcitriol can be useful in the combined treatment of patients suffering from colon cancer. In the present study we demonstrate, for the first time in an in vivo model system, the biological effect of combined therapy using 5-fluorouracil (5-FU) along with vitamin D analog PRI-2191 (tacalcitol, 1,24-dihydroxyvitamin D3) or PRI-2205 (5,6-trans-isomer of calcipotriol) on colon cancer. We investigated the influence of vitamin D analogs on the anticancer activity of 5-FU or capecitabine in the treatment of mice bearing MC38 mouse colon tumors implanted subcutaneously or orthotopically. The cell cycle distribution, E-cadherin expression and caspase 3/7 activity in vitro were also evaluated. We observed that both PRI-2191 and PRI-2205 significantly enhanced the antitumor activity of 5-FU; but these results depend on the treatment regimen. Applying the optimal schedule of combined therapy we observed a significant decrease in tumor growth, metastasis and also a prolongation of the survival time of mice, in comparison with the administrations of 5-FU given alone. Both combinations indicated a synergistic effect and did not cause toxicity. Moreover, analogs applied after completed course of administration of 5-FU, prolonged the antitumor effect of the drug. Furthermore, when the prodrug of 5-FU, capecitabine, was used, potentiation of its activity was also observed. Our data suggest that vitamin D analogs (especially PRI-2191) might be potentially applied to clinical use in order to enhance the anticancer effect of 5-FU and also prolong its activity against colon cancer. The activity of PRI-2191 is realized through stopping the cells in the G0/G1 cell cycle phase and increasing the expression of E-cadherin.Keywords
This publication has 47 references indexed in Scilit:
- Expression and Significance of Twist, E-Cadherin, and N-Cadherin in Gastrointestinal Stromal TumorsDigestive Diseases and Sciences, 2012
- The effect of season of operation on the survival of patients with resected non-small cell lung cancerInteractive CardioVascular and Thoracic Surgery, 2011
- Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008International Journal of Cancer, 2010
- Effects of potential calcium sensing receptor inducers on promoting chemosensitivity of human colon carcinoma cellsInternational Journal of Oncology, 2010
- Review and meta-analysis on vitamin D receptor polymorphisms and cancer riskCarcinogenesis: Integrative Cancer Research, 2009
- Use of combination therapy with cisplatin and calcitriol in the treatment of Y-79 human retinoblastoma xenograft modelBritish Journal of Ophthalmology, 2009
- Novel Gemini vitamin D3 analogs have potent antitumor activityThe Journal of Steroid Biochemistry and Molecular Biology, 2008
- Regulation of E‐cadherin and β‐catenin by Ca2+ in colon carcinoma is dependent on calcium‐sensing receptor expression and functionInternational Journal of Cancer, 2007
- Chemopreventive efficacy of 25-hydroxyvitamin D3 in colon cancerThe Journal of Steroid Biochemistry and Molecular Biology, 2007
- Vitamin D and prevention of colorectal cancerThe Journal of Steroid Biochemistry and Molecular Biology, 2005