Sahin Kazim, Cross Brian, Sahin Nurhan, Ciccone Karina, Suleiman Shadeah, Osunkoya Adeboye O, Master Viraj, Harris Wayne, Carthon Bradley, Mohammad Ramzi, Bilir Birdal, Wertz Karin, Moreno Carlos S, Walker Cheryl L, Kucuk Omer
Department of Animal Nutrition, Veterinary Faculty, Firat University, Elazig, Turkey.
Winship Cancer Institute, Emory University, Atlanta, GA, United States.
Arch Biochem Biophys. 2015 Apr 15;572:36-39. doi: 10.1016/j.abb.2015.01.006. Epub 2015 Jan 17.
Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80-85% of malignant renal tumors. Eker rat represents a unique animal model to study RCC since these rats develop spontaneous renal tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation resulting in the activation of the mammalian target of rapamycin (mTOR) pathway. This study examines the role of a lycopene-rich diet in the development of RCC in the TSC2 mutant Eker rat model. Ten-week old female Eker rats (n=90) were assigned in equal numbers to receive 0, 100 or 200mg/kg of lycopene as part of their daily diet. After 18 months the rats were sacrificed and the kidneys were removed. Immunohistochemical staining with antibodies against mTOR, phospho-S6 and EGFR were performed, as well as hematoxylin-eosin staining for histologic examination of the tumors. Tumors were counted and measured in individual kidneys. Presence of tumor decreased from 94% in control animals to 65% in the experimental group, but the difference was not statistically significant (P<0.12). However, mean numbers of renal carcinomas were statistically significantly decreased in the lycopene-treated rats (P<0.008) when compared to untreated controls. In the lycopene group, tumor numbers decreased (P<0.002) and the numbers tended to decrease linearly (P<0.003) as supplemental lycopene increased from 0 to 200. Control rats fed only basal diet had a greater length of tumors (23.98 mm) than rats fed lycopene supplement groups (12.90 mm and 11.07 mm) (P<0.05). Moreover tumor length decreased (P<0.02) and tumor length tended to decrease linearly (P<0.03) as supplemental lycopene increased from 0 to 200mg/kg. All tumors showed strong staining with antibodies against mTOR, phospho-S6 and EGFR. In conclusion, dietary supplementation with lycopene attenuates the development of renal cell cancers in the predisposed TSC2 mutant Eker rat model. These results suggest that lycopene may play a role in the prevention of RCC.
肾细胞癌（RCC）是人类最常见的上尿路癌症，占恶性肾肿瘤的80 - 85%。艾克大鼠是研究肾细胞癌的一种独特动物模型，因为这些大鼠会自发产生肾肿瘤和平滑肌瘤，这可能是由于结节性硬化症2（TSC2）突变导致哺乳动物雷帕霉素靶蛋白（mTOR）通路激活所致。本研究探讨了富含番茄红素的饮食在TSC2突变艾克大鼠模型中肾细胞癌发生发展中的作用。将90只10周龄雌性艾克大鼠平均分为三组，分别给予0、100或200mg/kg番茄红素作为日常饮食的一部分。18个月后处死大鼠并摘除肾脏。用抗mTOR、磷酸化S6和表皮生长因子受体（EGFR）抗体进行免疫组化染色，并进行苏木精 - 伊红染色以对肿瘤进行组织学检查。对每只肾脏中的肿瘤进行计数和测量。对照组动物的肿瘤发生率从94%降至实验组的65%，但差异无统计学意义（P<0.12）。然而，与未处理的对照组相比，番茄红素处理组大鼠的肾癌平均数量在统计学上显著减少（P<0.008）。在番茄红素组中，随着补充番茄红素从0增加到200，肿瘤数量减少（P<0.002）且呈线性下降趋势（P<0.003）。仅喂食基础饮食的对照大鼠的肿瘤长度（23.98mm）大于喂食番茄红素补充组的大鼠（12.90mm和11.07mm）（P<0.05）。此外，随着补充番茄红素从0增加到200mg/kg，肿瘤长度减少（P<0.02）且呈线性下降趋势（P<0.03）。所有肿瘤对抗mTOR、磷酸化S6和EGFR抗体均呈强染色。总之，在易患肾细胞癌的TSC2突变艾克大鼠模型中，饮食补充番茄红素可减轻肾细胞癌的发生发展。这些结果表明番茄红素可能在预防肾细胞癌中发挥作用。
