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Antitumor activity of mifepristone in the human LNCaP, LNCaP‐C4, and LNCaP‐C4‐2 prostate cancer models in nude mice
Author(s) -
El Etreby M. Fathy,
Liang Yayun,
Johnson Maribeth H.,
Lewis Ronald W.
Publication year - 2000
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(20000201)42:2<99::aid-pros3>3.0.co;2-i
Subject(s) - lncap , mifepristone , prostate cancer , medicine , endocrinology , prostate , androgen , cancer research , cancer , tumor progression , biology , hormone , pregnancy , genetics
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 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. Prostate 42:99–106, 2000. © 2000 Wiley‐Liss, Inc.