GROWTH-INHIBITORY EFFECTS OF 1,25-DIHYDROXYVITAMIN D-3 AND ITS SYNTHETIC ANALOG, -ENE-23YNE-26,27-HEXAFLUORO-19-NOR-CHOLECALCIFEROL (RO 25-6760), ON A HUMAN COLON-CANCER XENOGRAFT

The effect of 1,25-dihydroxyvitamin D-3 and its synthetic analogue, 1 -ene-23yne-26,27-hexafluoro-19-nor-cholecalciferol (Ro 25-6760), have been evaluated both in vitro and in vivo in human colorectal cancer ce ll lines expressing high (HT-29) and low (SW-620) levels of vitamin D receptor. 1,25-Dihydroxyvitamin D-3 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-d ihydroxyvitamin D, and Ro 25-6760 did not have any growth inhibitory e ffect on SW-620 at all concentrations. In mice with HT-29 tumor xenogr afts, administration of vitamin D at 0.1 and 0.2 mu g/injection i.p. t hree times/week did not cause any significant tumor growth delay, wher eas synthetic analogue Ro 25-6760, at both concentrations, caused a si gnificant tumor growth inhibition in comparison with the control arm. In 30% of mice treated by RO 25-6760 the tumors disappeared on average after the second injection, and tumor growth did not resume after dru g withdrawal. However, both 1,25-dihydroxyvitamin D, or Ro 25-6760 had no growth inhibitory effect at all applied concentrations in mice wit h the SW-620 tumor xenografts, The mechanism for this impressive growt h inhibition is not yet elucidated and warrants further investigation.