INHIBITION OF HT-29 HUMAN COLON-CANCER GROWTH UNDER THE RENAL CAPSULEOF SEVERE COMBINED IMMUNODEFICIENT MICE BY AN ANALOG OF 1,25-DIHYDROXYVITAMIN D-3, DD-003

An analogue of 1,25-dihydroxyvitamin D-3, 22(S)-24-homo-26,26,26,27, 2 7,27-hexafluoro-1 alpha 22,25-trihydroxyvitamin D-3 DD-003), showed 10 -fold greater inhibiting effect than 1,25-dihydroxyvitamin D-3 on the growth of HT-29 human colonic adenocarcinoma cells in culture. To exam ine the anticancer activity of DD-003 in vivo, a fibrin clot of HT-29 cells was prepared with fibrinogen and thrombin and implanted under th e renal capsule of the severe combined immunodeficient mouse. Starting 7 days after implantation of HT-29 tumor, mice were given 3 mu g/kg b ody weight of DD-003 or the vehicle i.p. every other day for 5 times. The HT-29 tumor grew rapidly in control mice; malignant growth was cle arly observed with mitosis, massive tumor angiogenesis, and invasion i nto normal kidney tissue. Tumors in DD-003 treated mice were smaller w ith less invasion compared to the control. Administration of DD-003 in hibited growth of HT-29 tumor by 63%. Serum calcium concentrations and body weights of the treated mice were similar to those of the control . DD-003 inhibited growth of HT-29 tumor in a dose-dependent manner ov er the range of 0.1-10 mu g/kg body weight, with no increase of serum calcium concentration observed at any dose level. When DD-003 was with drawn after 2 weeks of treatment, tumor growth resumed. Since chemosen sitivity tested by the subrenal capsule assay correlates web with clin ical response, DD-003 may be clinically applicable in procedures such as postsurgical chemotherapy of colon cancer.