Antitumor activity of (R,R')-4-methoxy-1-naphthylfenoterol in a @entity35 XXXX xenograft model in the @entity19 .

@entity19 @entity5 @entity36 @entity35 @entity463
(R,R')-4-methoxy-1-naphthylfenoterol (MNF) inhibits cancer cell proliferation in vitro through cell-type specific modulation of b2-adrenergic receptor and/or cannabinoid receptor function. Here, we report an investigation into antitumor activity of MNF in @entity35 @entity36 cells. The potent antiproliferative action of MNF in these cells (IC50 of    1 nmol/L) was refractory to pharmacological inhibition of b2-adrenergic receptor while a synthetic inverse agonist of cannabinoid receptor 1 significantly blocked MNF activity. The antitumor activity of MNF was then assessed in a C6 @entity463 xenograft model in @entity19 . Three days after subcutaneous implantation of C6 cells into the lower flank of @entity19 , these animals were subjected to i.p. injections of saline or MNF (2 mg/kg) for 19 days and @entity5 volumes were measured over the course of the experiment. Gene expression analysis, quantitative RT-PCR and immunoblot assays were performed on the @entity5 after treatment. Significant @entity5 volumes was observed in @entity19 receiving MNF when compared with the saline-treated group. We identified clusters in expression of genes involved in cellular proliferation, as well as molecular markers for @entity463 that were significantly downregulated in @entity5 of MNF-treated @entity19 as compared to saline-injected controls. The efficacy of MNF against @entity36 cell proliferation in vivo and in vitro was accompanied by marked reduction in the expression of cell cycle regulator proteins. This study is the first demonstration of MNF-dependent chemoprevention of a @entity463 xenograft model and may offer a potential mechanism for its anticancer action in vivo.
