The long-term objective of this application is to test the hypothesis that soybeans bioactive components inhibit the growth and metastasis of prostate cancer (CaP).
The specific aims are: 1) to evaluate the effects of soybean components on the growth and metastasis of an androgen-sensitive and PSA-producing human CaP cell line LNCaP, and an advanced and metastatic human CaP cell line PC-3 in vivo, and 2) To determine that soybean bioactive components inhibit the growth and metastasis of CaP tumors via inhibition of tumor angiogenesis. Male SCID mice will be inoculated intraprostatically with LNCaP or PC-3 cells, and assigned to one of the five soybean components-containing diets: 1) AIN-93M as control diet; 2) AIN-93 with isoflavone-depleted soy protein isolate, 3) AIN-93 with 0.7 percent of soy phytochemical concentrate, providing 800 mg genistein equivalents and 770mg daidzein equivalents/kg diet, 4) AIN-93 diet with 800mg genistein equivalents in the glycosylated form typically found in foods, or 5) AIN-93 diet with 770 mg daidzein equivalents/kg diet. At the end of experiment, primary tumor weight will be measured to determine prostatic tumor growth rate. We will quantitate the effects of dietary treatment on intraprostatic tumor growth and metastatic spread to the lymph nodes or lungs. We will first quantitate tumor proliferation index and apoptotic index which in prior studies show specific patterns of changes relative to microvessel density (factor VIII stainig). We will determine if VEGF, an angiogenic factor regulated by androgens and associated with prostate cancer progression, is inhibited by soy based diets. We will determine if circulating IGF-1 and androgens, both of which may modulate tumor angiogenesis and growth, are inhibited by soy treatments. Expression and activity of tumor metalloproteinases, critical regulators of tumor metastasis and angiogensis will be examined. Statistical analyses will be performed to answer the following questions: 1) if soy isoflavones are the major bioactive components inhibiting the growth and metastasis of prostate tumors; 2) if isoflavone-depleted soy protein has inhibitory effects on tumor growth and metastasis; 3) if other soybean phytochemicals have effects on tumor growth and metastasis; 4) if soybean bioactive components inhibit growth and/or metastasis of prostate tumors associated with regulations of angiogenesis-related biomarkers and/or other biomarkers. The proposed studies will provide new insight concerning the ability of bioactive components of soy to inhibit CaP progression. It is expencted that the results from proposed project will be translated to future clinical trials on CaP prevention/intervention.
| Zhou, Jin-Rong; Yu, Lunyin; Zerbini, Luiz F et al. (2004) Progression to androgen-independent LNCaP human prostate tumors: cellular and molecular alterations. Int J Cancer 110:800-6 |
| Zhou, Jin-Rong; Yu, Lunyin; Zhong, Ying et al. (2003) Soy phytochemicals and tea bioactive components synergistically inhibit androgen-sensitive human prostate tumors in mice. J Nutr 133:516-21 |
| Yu, Lunyin; Blackburn, George L; Zhou, Jin-Rong (2003) Genistein and daidzein downregulate prostate androgen-regulated transcript-1 (PART-1) gene expression induced by dihydrotestosterone in human prostate LNCaP cancer cells. J Nutr 133:389-92 |
| Zhou, Jin-Rong; Yu, Lunyin; Zhong, Ying et al. (2002) Inhibition of orthotopic growth and metastasis of androgen-sensitive human prostate tumors in mice by bioactive soybean components. Prostate 53:143-53 |
