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Anti-tumor activity of mycophenolate mofetil against human and mouse tumors in vivo

✍ Scribed by Robert J. Tressler; Laura J. Garvin; Doris L Slate

Publisher
John Wiley and Sons
Year
1994
Tongue
French
Weight
626 KB
Volume
57
Category
Article
ISSN
0020-7136

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✦ Synopsis

Cultured tumor cell lines, tumor xenografts grown in athymic nude mice, and a murine experimental metastasis model were used to assess the in vitro and in vivo anti-tumor activity of the potent IMP dehydrogenase (IMPDH) inhibitor, mycophenolic acid (MPA), and its morpholinoethyl ester pro-drug, mycophenotate mofetil (MM). The growth of all the cell lines tested was inhibited by MPA in vitro, with ECS0 values ranging from less than 0.1 pM to 3.9 pM. Mice were monitored for S.C. tumor outgrowth in the case of human tumor xenograft models or survival time for the murine experimental metastasis model. Treatment with MM p.0. was started 24 hr after tumor challenge or after tumors became palpable. Treatment of athymic nude mice bearing A3.0 I (T-lymphoblast), Molt4 (T-cell leukemia), CaPan-2 (pancreatic adenocarcinoma). CaLu-3 (non-smallcell lung adenocarcinoma), LS I74T and T84 (colon adenocarcinoma), and Daudi (B-cell lymphoma) human tumor xenografts with MM significantly inhibited S.C. tumor growth. Treatment of BALB/c mice with MM after i.v. injection of murine RAW1 17-H I 0 lymphoma cells in an experimental metastasis assay resulted in increased survival time for treated animals. No significant inhibitory effect on S.C. tumor outgrowth was seen with MM treatment of SK-Hep-I, a human hepatic endothelioma, or Hep-3B, a liver adenocarcinorna, at any of the doses tested.

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