Bladder Cancer Prevention by Silibinin

水飞蓟宾预防膀胱癌

• 批准号: 6576964
• 负责人: Rajesh Agarwal
• 金额: $ 7.57万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6576964
• 关键词: SDS polyacrylamide gel electrophoresis; antineoplastics; apoptosis; athymic mouse; binding proteins; biological signal transduction; bladder neoplasm; cancer prevention; cell growth regulation; cell proliferation; dietary supplements; enzyme linked immunosorbent assay; flavones; insulinlike growth factor; metastasis; neoplasm /cancer chemotherapy; neoplastic process; nonhuman therapy evaluation; phosphatidylinositol 3 kinase; protein protein interaction; protooncogene; tissue /cell culture; transcription factor; tumor necrosis factor alpha; urinary bladder epithelium; xenotransplantation

DESCRIPTION (provided by applicant): Bladder cancer is the most common type of cancer linked to occupational and environmental exposure to harmful chemical substances. Such substances are absorbed into bloodstream, filtered by kidneys, and stored in the bladder. Exposure of bladder tissue and lining to harmful substances eventually causes cancer. Standard treatment for bladder cancer includes surgery, chemo and radiation therapy, biological therapy, and combinations of these. However, surgery has undesirable physical and psychological effects, metastases are difficult to treat, and recurrence occurs. One approach to control bladder cancer growth and metastasis could be its prevention by phytochemicals; this approach has had a renewed public and scientific interest for the prevention of different epithelial cancers. Overall, human cancers appear to involve a gradual accumulation of genetic and epigenetic changes over a period of years. For example, alone or in combination, cell signaling, cell cycle and apoptosis regulators, and angiogenesis are identified as critical, perhaps causal, epigenetic events associated with tumor growth, progression and metastasis of several malignancies including bladder cancer. Together, these studies suggest that agents that could modulate these targets/events will be potent cancer preventive agents in general and bladder cancer in particular. Our recent studies in different human cancer cells show that silibinin inhibits cell signaling, modulates cell cycle regulators causing G1/G2-M arrest and leads to differentiation and/or apoptosis, and prevents skin and prostate cancers in mouse models. Together, hypothesis proposed is: silibinin is a novel bladder cancer preventive agent, and anti-cancer effect of silibinin involves inhibition of cell survival signaling leading to anti-proliferative and apoptotic efficacy. Following aims would establish bladder cancer preventive efficacy of silibinin. 1) To assess and define the effect of silibinin on cell survival signaling in normal bladder epithelial and bladder carcinoma HTB2 cells. 2) To assess and establish the efficacy of silibinin in human bladder carcinoma HTB2 xenograft growth and regression in nude mice. As a practical and translational approach, we believe that outcome of proposed studies will form a firm basis for a well-developed R01 grant to further define and establish the efficacy of silibinin against bladder cancer and the molecular mechanisms associated with its effects.

描述（由申请人提供）： 膀胱癌是与有害化学物质的职业和环境暴露有关的最常见癌症类型。这样的物质被吸收到血液中，被肾脏过滤并储存在膀胱中。膀胱组织和有害物质的衬里暴露最终会导致癌症。膀胱癌的标准治疗包括手术，化学疗法和放射治疗，生物疗法以及这些组合。但是，手术具有不良的身体和心理影响，转移很难治疗，并且会发生复发。控制膀胱癌生长和转移的一种方法可能是植物化学物质的预防。这种方法具有预防不同上皮癌的公开和科学兴趣。 总体而言，人类癌症似乎涉及多年来遗传和表观遗传变化的逐渐积累。例如，单独或组合，细胞信号传导，细胞周期和凋亡调节剂以及血管生成被确定为与肿瘤生长，进展和转移有关的几种恶性肿瘤（包括膀胱癌）的关键，可能是因果，表观遗传事件。总之，这些研究表明，可以调节这些靶标/事件的药物通常是有效的癌症预防剂，尤其是膀胱癌。 我们在不同人类癌细胞中的最新研究表明，硅酸盐素会抑制细胞信号，调节导致G1/G2-M停滞的细胞周期调节剂并导致分化和/或凋亡，并防止小鼠模型中的皮肤和前列腺癌。共同提出的假设是：硅酸盐是一种新型的膀胱癌预防剂，而抗癌蛋白的抗癌作用涉及抑制细胞存活信号传导，从而导致抗增殖和凋亡疗效。以下目标将确立膀胱癌的预防性硅酸盐素。 1）评估并定义了硅酸盐素对正常膀胱上皮和膀胱癌HTB2细胞中细胞存活信号传导的影响。 2）评估和确定米利宾蛋白在人膀胱癌HTB2异种移植的生长和裸鼠的消退的功效。 作为一种实用和转化的方法，我们认为拟议的研究的结果将构成良好发达的R01赠款的牢固基础，以进一步定义和确定硅酸盐针对膀胱癌的疗效以及与其作用相关的分子机制。