Universidade de São Paulo, Laboratory of Medical Investigation, Department of Urology (Lim55), São Paulo/SP, Brazil.
Clinics (Sao Paulo). 2011;66(12):2121-4. doi: 10.1590/s1807-59322011001200019.
Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer.
Tumor implantation was achieved in six- to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA.
Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model.
Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer.
吸烟是膀胱癌发展的主要危险因素。在吸烟的这种作用的介质中有一种是核因子-κB。姜黄素通过下调核因子-κB 的活性来抑制细胞转化。普马-1 是一种在人类肿瘤细胞中诱导细胞凋亡的化合物，恢复突变型 p53 的功能。我们的研究旨在评估姜黄素和普马-1 在膀胱癌动物模型中的作用。
通过将 MB49 膀胱癌细胞注入膀胱，在 6-8 周龄的雌性 C57BL/6 小鼠中实现肿瘤植入。在第 2、6、10 和 14 天对膀胱内用姜黄素和普马-1 进行治疗。第 15 天，处死动物。免疫组织化学用于确定细胞周期蛋白 D1、Cox-2 和 p21 的表达。使用 PCNA 检查细胞增殖。
用姜黄素治疗的动物比其他组的动物表现出更高程度的坏死。免疫组织化学显示姜黄素处理组细胞周期蛋白 D1 的表达减少。用姜黄素处理的所有小鼠细胞均为 p21 阳性，表明该化合物诱导了 p53 途径。普马-1 未引起肿瘤大小、坏死、细胞增殖或与 p53 途径相关的蛋白质表达的任何变化。
姜黄素在该动物膀胱癌模型中表现出活性，可能通过调节核因子-κB 和 p53 起作用。因此，姜黄素是作为卡介苗替代物治疗浅表膀胱癌临床试验的良好选择。相比之下，普马-1 似乎对膀胱癌没有影响。
