TZT-1027 Elucidates Antitumor Activity through Direct Cytotoxicity and Selective Blockade of Blood Supply

Background: TZT-1027 is a newly developed antitumor agent derived from dolastatin 10. Materials and Methods: The in vitro activity of TZT-1027 on MCF-7 and R-27 cells was evaluated by MTT assay. TZT-1027 1 mg/kg/week was administered i.v. for 4 weeks into nude mice bearing MCF-7 and R-27. Subsequent...

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Bibliographic Details
Published in:Anticancer research 2004-07, Vol.24 (4), p.2201-2208
Main Authors: HASHIGUCHI, Naoko, KUBOTA, Tetsuro, KOBAYASHI, Motohiro, KOH, Jun-Ichi, YAMADA, Yoshinori, SAIKAWA, Yoshiro, OTANI, Yoshihide, WATANABE, Masahiko, KUMAI, Koichiro, KITAJIMA, Masaki, WATANABE, Jun-Ichi
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Biological and medical sciences
Breast Neoplasms - blood supply
Breast Neoplasms - drug therapy
Cell Line, Tumor
Dose-Response Relationship, Drug
Female
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasms, Hormone-Dependent - blood supply
Neoplasms, Hormone-Dependent - drug therapy
Neovascularization, Pathologic - drug therapy
Oligopeptides - pharmacology
Taxoids - pharmacology
Tumors
Xenograft Model Antitumor Assays
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Summary:Background: TZT-1027 is a newly developed antitumor agent derived from dolastatin 10. Materials and Methods: The in vitro activity of TZT-1027 on MCF-7 and R-27 cells was evaluated by MTT assay. TZT-1027 1 mg/kg/week was administered i.v. for 4 weeks into nude mice bearing MCF-7 and R-27. Subsequently, primary cultured cells from xenografts were also used for CD-DST. Two mg of TZT-1027 or 40 mg docetaxel per kg were injected i.v. into nude mice bearing R-27. 0.2% Evans blue was injected to assess the blood flow. Results: TZT-1027 suppressed the in vitro growth of MCF-7 cells, while R-27 cells were resistant to TZT-1027, although its in vivo antitumor activity was remarkable. TZT-1027 blockaded R-27 tumor blood flow immediately after injection; blood flow was not affected by docetaxel. Conclusion: TZT-1027 exerts its antitumor activity through direct cytotoxicity against MCF-7 cells and through selective blockade of tumor blood flow against R-27 cells.
ISSN:0250-7005
1791-7530