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.
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.
Evans
S R
SR
Department of Surgery, George Washington University Medical Center, Washington, DC 20037, USA. sursre@gwumc.edu
Schwartz
A M
AM
Shchepotin
E I
EI
Uskokovic
M
M
Shchepotin
I B
IB
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002117:Calcitriol / Q000031:analogs & derivatives / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C113532:Ro 25-6760; D002762:Cholecalciferol; D002117:Calcitriol; D002118:Calcium