Inhibition of orthotopic growth and metastasis of androgen-sensitive human prostate tumors in mice by bioactive soybean components.
Inhibition of orthotopic growth and metastasis of androgen-sensitive human prostate tumors in mice by bioactive soybean components.
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生物活性大豆成分抑制小鼠体内雄激素敏感的人类前列腺肿瘤的原位生长和转移。
DOI：
10.1002/pros.10141
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
Blackburn,GeorgeL
中科院分区：
文献类型：
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作者：
Zhou,Jin-Rong;Yu,Lunyin;Zhong,Ying;Nassr,RenaL;Franke,AdrianA;Gaston,SandraM;Blackburn,GeorgeL
研究背景在人群中系统分析饮食对前列腺癌发生和发展的影响通常是困难的，因为饮食变量与遗传背景和社会行为的多样性重叠。模拟人类前列腺癌的动物模型允许对显示抗前列腺癌活性的营养剂的作用机制进行实验分析。方法我们使用原位植入模型来表征雄激素敏感性LNCaP前列腺肿瘤对三种良好表征的大豆膳食补充剂的体内反应：大豆植物化学浓缩物（SPC），在原位植入雄激素敏感的人前列腺细胞系LNCaP的雄性SCID小鼠中，大豆蛋白，染料木苷，与对照组相比，SPC组肿瘤重量分别降低42%（P= 0.07）、57%（P< 0.05）和70%（P< 0.005）。所有三种大豆补充剂都显著增加了肿瘤细胞凋亡，降低了微血管密度，而肿瘤增殖没有显著变化。每种补充剂都产生了不同的血清雄激素反应，染料木黄酮使血清总睾酮和双氢睾酮（DHT）降低最多（P< 0.05），睾酮与双氢睾酮比值增加最多（P< 0.05），大豆蛋白使生物活性雄激素降低最多（P< 0.05）。只有SPC显着抑制转移到淋巴结和肺，只有SPC产生了显着增加肿瘤p53 expression. CONCLUSION总之，这些数据表明，抗前列腺癌活性的饮食大豆蛋白，大豆植物化学物质，染料木苷使用不同的分子途径。此外，我们已经证明，这种动物模型可用于设计前列腺癌预防和治疗的饮食策略。前列腺53：143-153，2002年。© 2002 Wiley利斯公司
BACKGROUNDSystematic analysis of the influence of diet on the initiation and progression of prostate cancer is often difficult in human populations, for which dietary variables overlap a diversity of genetic backgrounds and social behaviors. Animal models that emulate human prostate cancer allow experimental analysis of the mechanisms of action of nutritional agents that show anti‐prostate cancer activity.METHODSWe have used an orthotopic implant model to characterize the in vivo response of androgen‐sensitive LNCaP prostate tumors to three well‐characterized soy dietary supplements: isoflavone depleted soy protein, soy phytochemical concentrate (SPC), and genistin.RESULTSIn male SCID mice orthotopically implanted with the androgen‐sensitive human prostate cell line LNCaP, dietary supplements of soy protein, genistin, and SPC reduced primary tumor weight by 42% (P= 0.07), 57% (P< 0.05) and 70% (P< 0.005), respectively. All three soy supplements significantly increased tumor apoptosis and decrease microvessel density, with no significant change in tumor proliferation. Each supplement produced a distinct serum androgen response, with genistin producing the greatest decrease in total serum testosterone and dihydrotestosterone (DHT) (P< 0.05) and the greatest increase in testosterone to DHT ratio (P< 0.05) and soy protein the greatest decrease in bioactive androgen (P< 0.05). Only SPC significantly inhibited metastases to lymph nodes and lungs, and only SPC produced a significant increase in tumor p53 expression.CONCLUSIONTaken together, these data suggest that the anti‐prostate cancer activity of dietary soy protein, soy phytochemicals, and genistin use different molecular pathways. In addition, we have demonstrated that this animal model can be used in the design of dietary strategies for prostate cancer prevention and therapy. Prostate 53: 143–153, 2002. © 2002 Wiley‐Liss, Inc.