Bortel Nicola, Armeanu-Ebinger Sorin, Schmid Evi, Kirchner Bettina, Frank Jan, Kocher Alexa, Schiborr Christina, Warmann Steven, Fuchs Jörg, Ellerkamp Verena
Department of Pediatric Surgery and Pediatric Urology, University Hospital Tuebingen, D-72076 Tuebingen, Germany.
Institute of Biological Chemistry and Nutrition, University of Hohenheim, Division of Biofunctionality and Safety of Food, D-70599 Stuttgart, Germany.
Oncotarget. 2015 Dec 1;6(38):40680-91. doi: 10.18632/oncotarget.5673.
In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC.
在儿童肝细胞癌（pHCC）患者中，5年总生存率较低。由于化疗耐药性和肿瘤复发，顺铂和阿霉素等细胞毒性疗法的效果有限。在成人肝癌中，已描述了姜黄素使用的几种抗肿瘤特性。姜黄素是辅助肿瘤学中研究最充分的植物化学物质之一，且无相关副作用。其应用因生物利用度低而受到限制。关于姜黄素对小儿上皮性肝脏恶性肿瘤的影响知之甚少。我们研究了姜黄素与顺铂联合对两种小儿上皮性肝肿瘤细胞系的作用。确定了其作用机制为抑制NFκB、β-连环蛋白以及降低细胞周期蛋白D。使用小鼠异种移植模型，我们发现口服胶束姜黄素和顺铂联合治疗后甲胎蛋白显著降低。口服胶束姜黄素后，在血样、器官裂解物和肿瘤组织中发现了显著浓度的姜黄素类化合物。胶束姜黄素与顺铂联合可能是治疗小儿肝癌的一种有前景的策略。
