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.


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.


CONCLUSIONS
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.
Hashiguchi
Naoko
N
Department of Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Kubota
Tetsuro
T
Koh
Jun-Ichi
J
Yamada
Yoshinori
Y
Saikawa
Yoshiro
Y
Otani
Yoshihide
Y
Watanabe
Masahiko
M
Kumai
Koichiro
K
Kitajima
Masaki
M
Watanabe
Jun-Ichi
J
Kobayashi
Motohiro
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009842:Oligopeptides / Q000494:pharmacology*; D043823:Taxoids / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D009842:Oligopeptides; D043823:Taxoids; D000077143:Docetaxel; C105791:soblidotin