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Experimental Therapeutics

Inhibition of HT-29 Human Colon Cancer Growth under the Renal Capsule of Severe Combined Immunodeficient Mice by an Analogue of 1,25-Dihydroxyvitamin D3, DD-003

Yoko Tanaka, An-Ya S. Wu, Nobuo Ikekawa, Katsuhiko Iseki, Makoto Kawai and Yoshiro Kobayashi
Yoko Tanaka
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An-Ya S. Wu
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Nobuo Ikekawa
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Katsuhiko Iseki
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Makoto Kawai
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Yoshiro Kobayashi
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DOI:  Published October 1994
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Abstract

An analogue of 1,25-dihydroxyvitamin D3, 22(S)-24-homo-26,26,26,27,27,27-hexafluoro-1α,22,25-trihydroxyvitamin D3 (DD-003), showed 10-fold greater inhibiting effect than 1,25-dihydroxyvitamin D3 on the growth of HT-29 human colonic adenocarcinoma cells in culture. To examine the anticancer activity of DD-003 in vivo, a fibrin clot of HT-29 cells was prepared with fibrinogen and thrombin and implanted under the renal capsule of the severe combined immunodeficient mouse. Starting 7 days after implantation of HT-29 tumor, mice were given 3 µg/kg body 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 clearly observed with mitosis, massive tumor angiogenesis, and invasion into normal kidney tissue. Tumors in DD-003 treated mice were smaller with less invasion compared to the control. Administration of DD-003 inhibited 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 over the range of 0.1–10 µg/kg body weight, with no increase of serum calcium concentration observed at any dose level. When DD-003 was withdrawn after 2 weeks of treatment, tumor growth resumed. Since chemosensitivity tested by the subrenal capsule assay correlates well with clinical response, DD-003 may be clinically applicable in procedures such as postsurgical chemotherapy of colon cancer.

Footnotes

  • ↵1 Supported in part by the Department of Veterans Affairs Medical Center, Research Service, and Albany Research Institute, Albany, NY.

  • ↵2 To whom requests for reprints should be addressed, at Veterans Affairs Medical Center (151), 113 Holland Avenue, Albany, NY 12208.

  • Received May 2, 1994.
  • Accepted August 4, 1994.
  • ©1994 American Association for Cancer Research.
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October 1994
Volume 54, Issue 19
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Inhibition of HT-29 Human Colon Cancer Growth under the Renal Capsule of Severe Combined Immunodeficient Mice by an Analogue of 1,25-Dihydroxyvitamin D3, DD-003
Yoko Tanaka, An-Ya S. Wu, Nobuo Ikekawa, Katsuhiko Iseki, Makoto Kawai and Yoshiro Kobayashi
Cancer Res October 1 1994 (54) (19) 5148-5153;

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Inhibition of HT-29 Human Colon Cancer Growth under the Renal Capsule of Severe Combined Immunodeficient Mice by an Analogue of 1,25-Dihydroxyvitamin D3, DD-003
Yoko Tanaka, An-Ya S. Wu, Nobuo Ikekawa, Katsuhiko Iseki, Makoto Kawai and Yoshiro Kobayashi
Cancer Res October 1 1994 (54) (19) 5148-5153;
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