以肝癌細胞 (HepG2) 探討臺灣產南美假櫻桃果實乙醇萃取物調控鎳誘導 VEGF 之表現

Study on Regulation of Ethanolic Extract from Jamaica Cherry (Muntingia calabura Linn.) Fruits Gathered in Taiwan on VEGF Expressions Induce by Nickel in Hepatocellular Carcinoma Cells (HepG2)

郭麗淳(Li-Chun Kuo)

指導教授 ： 林昭田 ； 楊登傑

中山醫學大學/健康管理學院/健康餐飲暨產業管理學系碩士班/碩士(2016年)

摘要

南美假櫻桃 (Muntingia calabura Linn.)，為文丁科 (Muntingiaceae) 西印度櫻桃屬 (Muntingia) 之植物。原產於美洲熱帶，在 1936 年引入台灣，主要分布在低海拔地區。在臺灣多作為行道樹或庭園樹之用，先前的研究多著重於葉，對於可直接食用的果實並無深入地探討。在我們之前的研究中發現，臺灣產南美假櫻桃果實經由乙醇萃取，可得到較高的萃取率及酚類化合物，且抗氧化效果亦較佳 (陳，2016)；在以脂多醣誘發 RAW264.7 (小鼠巨噬細胞) 發炎模式中，也發現臺灣產南美假櫻桃果實乙醇萃取物具有抗發炎的功效 (沈，2015)。而在科技蓬勃發展的現在，鎳良好的金屬特性，使其被廣泛運用於我們生活周遭，卻也帶來了環境汙染及健康危害。因此，本研究以人類肝癌細胞 HepG2 模式探討臺灣產南美假櫻桃果實乙醇萃取物調控鎳誘導血管內皮生長因子 (vascular endothelial growth factor, VEGF) 之表現。先前研究中已有動物實驗證實抑制 VEGF 表現可以抑制腫瘤的生長 (Blouw et al., 2003)，顯示 VEGF 在腫瘤的生長過程中扮演舉足輕重的角色。從我們的實驗結果中發現，隨著臺灣產南美假櫻桃果實乙醇萃取物濃度的增加，能抑制 hypoxia-inducible factor 1-alpha (HIF-1α) 蛋白表現量，進而抑制細胞激素 VEGF 的釋放，使 VEGF 與 vascular endothelial growth factor receptor (VEGFR) 結合受到抑制，導致下游 signal transducer and activator of transcription 3 (STAT3) 的活化被抑制。實驗結果證實臺灣產南美假櫻桃果實乙醇萃取物能有效抑制鎳誘發的細胞增生作用之發生，進而降低人類肝癌細胞 (HepG2) 增生之能力。

關鍵字

南美假櫻桃 ； HepG2 ； VEGF ； HIF-1α ； STAT3

並列摘要

Jamaica cherry (Muntingia calabura Linn.) belongs to the family Muntingiaceae, a plant originated in tropical America. It was introduced into Taiwan in 1936, and mainly at low altitudes. In Taiwan, it is often planted as street trees or for gardening purposes. Previous studies usually focused on its leaves, whereas detailed studies for the edible parts of the fruit are still lacking. Our previous studies have shown that ethanolic extract from Jamaica cherry (Muntingia calabura Linn.) fruits gathered in Taiwan has abundant phenolic compounds, may exhibited good antioxidant capacity and anti-inflammatory effect (Chen, 2016；Shen, 2015). In science and technology booming now, the nickel metal good characteristics, it is widely used in our lives around, but it also brought pollution and hazards. Therefore, the present study to investigate the performance of ethanolic extract from Jamaica cherry (Muntingia calabura Linn.) fruits gathered in Taiwan on vascular endothelial growth factor (VEGF) expressions induced by nickel in hepatocellular carcinoma cells (HepG2). Animal experiments have been demonstrated to inhibit VEGF expression can inhibit tumor growth (Blouw et al., 2003), show that VEGF indeed play an important role in the growth of tumors. It was found that, with the increase of ethanolic extract from Jamaica cherry (Muntingia calabura Linn.) fruits gathered in Taiwan can inhibit the expression level of hypoxia-inducible factor 1-alpha (HIF-1α), and inhibit the release of cytokines VEGF, so that VEGF and vascular endothelial growth factor receptor (VEGFR) binding was inhibited, thereby inhibiting downstream of signal transducer and activator of transcription 3 (STAT3) activation, the occurrence of nickel-induced angiogenesis inhibition effect of reach. In our data confirmed that ethanolic extract from Jamaica cherry (Muntingia calabura Linn.) fruits gathered in Taiwan can reduce the hepatocellular carcinoma cells (HepG2) proliferation by NiCl2.

並列關鍵字

Jamaica cherry ； HepG2 ； Vascular endothelial growth factor (VEGF) ； Hypoxia-inducible factor 1-alpha (HIF-1α) ； Signal transducer and activator of transcription 3 (STAT3)

參考文獻

鍾志明。2010。常見野生美味果樹南美假櫻桃之介紹。農業試驗所技術服務。83，5-8。

沈柏言。2015。以脂多醣誘發 RAW264.7 小鼠巨噬細胞發炎模式探討台灣產南美假櫻桃乙醇萃取物的抗發炎功效。中山醫學大學健康餐飲暨產業管理學系研究所。碩士論文。

陳廷祐。2016。台灣產南美假櫻桃果實主要抗氧化成分之分離與鑑定。中山醫學大學醫學應用化學系研究所。碩士論文。

Poonkothai, M. and Shyamala Vijayavathi, B. (2012). Nickel as an essential element and a toxicant. International Journal of Environmental, 1, 285-288.

Pan, J. J., Chang, Q. S., Wang, X., Son, Y. O., Liu, J., Zhang, Z., Bi, Y. Y., and Shi, X. (2011). Activation of Akt/GSK3beta and Akt/Bcl-2 signaling pathways in nickel-transformed BEAS-2B cells. International Journal of Oncology, 39, 1285-1294.