Antitumor activity of mifepristone in the human LNCaP, LNCaP-C4, and LNCaP-C4-2 prostate cancer models in nude mice

M. Fathy El Etreby, Yayun Liang, Maribeth H Johnson, Ronald W Lewis

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

BACKGROUND. Antiprogestins are a promising new class of mammary tumor inhibitors with a unique mechanism of action. Previously published results also suggest a tumor-inhibitory effect of antiprogestins in prostate cancer models. The objective of the present studies was to determine whether androgen-sensitive and androgen-insensitive variants of the well- characterized LNCaP human prostate cancer cell line exhibit stable differences in their sensitivity to in vivo antitumor activity of the antiprogestin, mifepristone. METHODS. Exponentially growing LNCaP, LNCaP-C4, and LNCaP-C4-2 prostate cancer cells in culture were mixed with Matrigel and injected subcutaneously (s.c.) into the flank of 6-8-week-old male nude mice. The tumors were permitted to grow until they reached a volume of 270-300 mm3. The animals were then randomly assigned to two groups. One group received mifepristone (50 mg/kg/day s.c.). Control animals were treated with vehicle. Tumor volume was determined every 4 days. After 28 days of treatment, the tumors were harvested and wet weights were determined. RESULTS. The inoculated tumor cells produced progressively growing tumors in male nude mice. However, the androgen-insensitive LNCaP-C4-2 cells showed the most aggressive and most rapid growth rate and shortest time to tumor progression. The tumors derived from the LNCaP-C4 cells exhibited a higher rate of tumor growth as compared with those derived from the parental androgen-sensitive LNCaP cells. In all three models, mifepristone treatment caused a significant retardation of tumor progression: after 28 days of treatment, about 50% inhibition of tumor weight was observed in the mifepristone treatment groups (P < 0.05) compared with the corresponding control groups. CONCLUSIONS. This is the first report demonstrating significant antitumor activity of mifepristone in both androgen-sensitive and androgen-insensitive variants of the LNCaP human prostate cancer model in nude mice. These results suggest a potential clinical benefit of the use of antiprogestins as a novel nonandrogen ablation therapeutic approach in the management of prostate cancer.

Original languageEnglish (US)
Pages (from-to)99-106
Number of pages8
JournalProstate
Volume42
Issue number2
DOIs
Publication statusPublished - Jan 31 2000

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Keywords

  • Antiprogestins (mifepristone)
  • LNCaP cells
  • Nude mice
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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