Potentiation of docetaxel antitumor activity by batimastat against mouse forestomach carcinoma.
Docetaxel is a chemical compound belonging to the taxoid class of anticancer agents. Batimastat (BB-94) is the first matrix metalloproteinase inhibitor entering clinical trials. To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat on mouse forestomach carcinoma (MFC), and compared them with doxorubicin. In vitro growth curve analysis, MTT assay, and clonogenic assay were used to determine the cytotoxic effect of docetaxel or/and BB-94 on MFC. They showed that docetaxel, but not BB-94, had a significant cytotoxicity and that the effect of docetaxel was not enhanced by BB-94. In an early stage MFC tumor model, an obvious antitumor effect of docetaxel or doxorubicin given iv at maximum tolerated dose (MTD) was observed. Tumor growth inhibition was greater for docetaxel + BB-94 (96.0%) than for doxorubicin + BB-94 (88.0%), docetaxel (89.0%), doxorubicin (68.0%), and BB-94 (33.0%). Docetaxel showed activity against advanced stage MFC tumor in a dose-dependent manner and was more effective at MTD than doxorubicin, with 4/5 regression, 46.5 days tumor growth delay, and 2.8 log10 tumor-cell kill. Our results suggest that docetaxel is an effective new cytotoxic drug against MFC tumor and that BB-94 enhances the antitumor activity of docetaxel in the dose and schedule used.
Gu
B
B
Department of Clinical Pharmacology, North Taiping Road Hospital, Beijing, China.
Wu
D
D
Li
M
M
Lü
H
H
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology
D043823:Taxoids; D013876:Thiophenes; D000077143:Docetaxel; D010649:Phenylalanine; C080985:batimastat; D017239:Paclitaxel