Antitumor activity of mifepristone in the human LNCaP, LNCaP-C4, and LNCaP-C4-2 prostate cancer models in nude mice
✍ Scribed by El Etreby, M. Fathy; Liang, Yayun; Johnson, Maribeth H.; Lewis, Ronald W.
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 144 KB
- Volume
- 42
- Category
- Article
- ISSN
- 0270-4137
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✦ Synopsis
BACKGROUND.
Antiprogestins are a promising new class of mammary tumor inhibitors with a unique mechanism of action. Previously published results also suggest a tumorinhibitory 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 mm 3 . 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.