5518

Bladder cancer is the fifth most common malignancy diagnosed in the United States. With the unknown etiological factors for bladder cancer carcinogenesis and the fact that bladder cancer patients are facing both threat of metastases and uncontrolled local recurrence after treatment, additional efforts to define dietary intervention or chemoprevention programs for bladder cancer progression/recurrence and metastasis are urgently needed. A role of diet and nutrition in bladder cancer development and progression is biologically plausible since most substances or metabolites are excreted through the urinary tract, and are consequently in direct contact with the mucosa of the bladder. In previous studies we have shown that soy bioactive components significantly inhibit the bladder cancer cell growth both in vitro and in an orthotopic bladder tumor model. Mice treated with genistin and the genistein-rich soy phytochemical concentrate (SPC) had reduced final tumor weights by 56% (P<0.05) and 52% (P<0.05) respectively, associated with induction of tumor cell apoptosis and inhibition of tumor angiogenesis in vivo. In addition, SPC treatment, but not genistin treatment, significantly inhibited lung metastases by 95% (P<0.01). To further investigate the molecular mechanisms behind anti-growth and anti-metastasis of soy components, we performed microarray assays by using the tumor samples. Total RNA was extracted by using RNeasy Mini Kit From Qiagen Inc. First and second strand cDNA were synthesized from 5-15mg of total RNA using superscript double stranded cDNA synthesis kit and oligo-dt24-T7 primer according to the manufacturer's instructions. Affymetrix microarray assay was performed in HG-U133 plus 2.0 arrays. Data were analyzed by using Affymetrix Netafex analysis as well as cluster analysis. We observed differential expression of certain genes that are specifically related to angiogenesis, cell cycle, apoptosis and metastasis between the treated and the control groups. We also identified several new candidate genes whose activities in bladder cancer were not previously reported. We are performing gene function assays to determine the functional roles of these modulated genes in anti-growth and anti-metastasis activities of soy bioactive components.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]