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Growth inhibitory effects of 1,25-dihydroxyvitamin D3 and its synthetic analogue, 1alpha,25-dihydroxy-16-ene-23yne-26,27-hexafluoro-19-nor-cholecalcifero l (Ro 25-6760), on a human colon cancer xenograft.

Abstract
The effect of 1,25-dihydroxyvitamin D3 and its synthetic analogue, 1alpha,25-dihydroxy-16-ene-23yne-26,27-hexafluoro-19-n or-cholecalciferol (Ro 25-6760), have been evaluated both in vitro and in vivo in human colorectal cancer cell lines expressing high (HT-29) and low (SW-620) levels of vitamin D receptor. 1,25-Dihydroxyvitamin D3 caused significant dose-dependent growth inhibition of HT-29 cells at concentrations ranging from 10(-11) to 10(-6). The antiproliferative effect of Ro 25-6760 on HT-29 cells was also dose-dependent with cell counts on day 6, ranging from 98% of control at 10(-11) M to 14% of control at 10(-6) M. However, 1,25-dihydroxyvitamin D3 and Ro 25-6760 did not have any growth inhibitory effect on SW-620 at all concentrations. In mice with HT-29 tumor xenografts, administration of vitamin D at 0.1 and 0.2 microg/injection i.p. three times/week did not cause any significant tumor growth delay, whereas synthetic analogue Ro 25-6760, at both concentrations, caused a significant tumor growth inhibition in comparison with the control arm. In 30% of mice treated by R0 25-6760 the tumors disappeared on average after the second injection, and tumor growth did not resume after drug withdrawal. However, both 1,25-dihydroxyvitamin D3 or Ro 25-6760 had no growth inhibitory effect at all applied concentrations in mice with the SW-620 tumor xenografts. The mechanism for this impressive growth inhibition is not yet elucidated and warrants further investigation.
AuthorsS R Evans, A M Schwartz, E I Shchepotin, M Uskokovic, I B Shchepotin
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 4 Issue 11 Pg. 2869-76 (Nov 1998) ISSN: 1078-0432 [Print] United States
PMID9829754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Ro 25-6760
  • Cholecalciferol
  • Calcitriol
  • Calcium
Topics
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Calcitriol (analogs & derivatives, therapeutic use)
  • Calcium (blood, metabolism)
  • Cell Division (drug effects)
  • Cholecalciferol (analogs & derivatives, therapeutic use)
  • Colonic Neoplasms (drug therapy, metabolism)
  • Female
  • HT29 Cells
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Tumor Cells, Cultured

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