[In vitro direct antiproliferative activity and in vivo antitumor activity of bropirimine against bladder cancer].
Bropirimine is an antitumor agent currently used in clinical trials on bladder cancer. It is known to induce IFN, to activate NK cells and to inhibit the growth of tumor cells. In this study, we examined the in vitro and in vivo efficacy of bropirimine on human and murine bladder cancer. Bropirimine showed in vitro antiproliferative activity on the human bladder cancer cell lines, T 24 and KoTCC-1. This activity was not: affected by the neutralizing antibodies against IFN-alpha, TNF-alpha or IL-1 beta, indicating it is the direct activity of bropirimine without involvement of cytokine production by tumor cells. Bropirimine was active at the concentrations comparable to those in serum or urine attained in clinical trials, which suggests that this direct antiproliferative activity is one of the important antitumor mechanisms of bropirimine. In in vivo experiments, bropirimine reduced the growth of transplanted murine MBT-2 and human KoTCC-1 bladder cancers by oral administration every 4 days starting on day 1, but did not show efficacy when the drug treatment was started on day 8. The antitumor activity of bropirimine was dependent on the timing for drug treatment initiation.
Tahara
M
M
Tsukuba Research Laboratories, Upjohn Pharmaceuticals Limited.
Nomura
S
S
Takahashi
M
M
Takagi
H
H
Hashimoto
M
M
Eto
H
H
Kamidono
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology*
D000970:Antineoplastic Agents; D003596:Cytosine; C033560:bropirimine