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.