Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways.
Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways.
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DOI：
10.18632/oncotarget.5673
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Ellerkamp V
中科院分区：
文献类型：
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作者：
Bortel N;Armeanu-Ebinger S;Schmid E;Kirchner B;Frank J;Kocher A;Schiborr C;Warmann S;Fuchs J;Ellerkamp V
儿童肝细胞癌（pHCC）的5年总生存率很低。由于化疗耐药和肿瘤复发，细胞抑制疗法如顺铂和阿霉素的效果有限。在成人HCC中，姜黄素的几种抗肿瘤特性被描述。姜黄素是互补肿瘤学中研究最多的植物化学物质之一，没有相关的副作用。其使用受到低生物利用度的限制。姜黄素对儿童上皮性肝恶性肿瘤的影响尚不清楚。我们研究了姜黄素联合顺铂对两种儿童上皮性肝肿瘤细胞系的影响。作为作用机制的抑制NFkappaB， β -连环蛋白和细胞周期蛋白D的降低被确定。使用小鼠异种移植模型，我们可以显示口服胶束姜黄素和顺铂联合治疗后甲胎蛋白显著降低。在口服胶束姜黄素后，在血液样本、器官裂解物和肿瘤组织中发现了显著浓度的姜黄素。胶束姜黄素联合顺铂治疗小儿肝细胞癌是一种很有前景的治疗策略。
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.