Lim Ji Ye, Kim Yoo-Sun, Kim Kyung-Mi, Min Soo Jin, Kim Yuri
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Republic of Korea.
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 120-750, Republic of Korea.
Biochem Biophys Res Commun. 2014 Aug 8;450(4):1475-80. doi: 10.1016/j.bbrc.2014.07.021. Epub 2014 Jul 11.
Neuroblastoma (NB) is the most common extracranial solid cancer in young children and malignant NB cells have been shown to possess cancer stem cell (CSC) characteristics. Thus, the successful elimination of CSCs represents a strategy for developing an effective preventive and chemotherapeutic agent. CSCs are characterized by differentiation and tumorigenicity. β-Carotene (BC) has been associated with many anticancer mechanisms, although the efficacy of BC on CSCs remains unclear. In the present study, the effects of BC on tumor cell differentiation and tumorigenicity was investigated using a xenograft model. Mice were pretreated with BC for 21 days, then received a subcutaneous injection of SK-N-BE(2)C cells. Both tumor incidence and tumor growth were significantly inhibited for mice that received BC supplementation compared to the control group. Treatment with BC has also been shown to induce tumor cell differentiation by up-regulating differentiation markers, such as vimentin, peripherin, and neurofilament. Conversely, BC treatment has been shown to significantly suppress tumor stemness by down-regulating CSC markers such as Oct 3/4 and DLK1. BC treatment also significantly down-regulated HIF1-α expression and its downstream target, vascular endothelial growth factor (VEGF). Taken together, these results suggest that BC is a potential chemotherapeutic reagent for the treatment of NB, and mediates this effect by regulating the differentiation and stemness of CSCs, respectively.
神经母细胞瘤（NB）是幼儿中最常见的颅外实体癌，并且已证明恶性NB细胞具有癌症干细胞（CSC）特征。因此，成功消除CSCs是开发有效预防和化疗药物的一种策略。CSCs的特征在于分化和致瘤性。β-胡萝卜素（BC）与许多抗癌机制有关，尽管BC对CSCs的功效仍不清楚。在本研究中，使用异种移植模型研究了BC对肿瘤细胞分化和致瘤性的影响。小鼠先用BC预处理21天，然后皮下注射SK-N-BE(2)C细胞。与对照组相比，接受BC补充的小鼠的肿瘤发生率和肿瘤生长均受到显著抑制。BC治疗还显示通过上调分化标志物（如波形蛋白、外周蛋白和神经丝）来诱导肿瘤细胞分化。相反，BC治疗已显示通过下调CSC标志物（如Oct 3/4和DLK1）来显著抑制肿瘤干性。BC治疗还显著下调HIF1-α表达及其下游靶点血管内皮生长因子（VEGF）。综上所述，这些结果表明BC是一种治疗NB的潜在化疗试剂，并分别通过调节CSCs的分化和干性来介导这种作用。
