銀杏萃取物和柴胡皂苷 a 對 HA 22T/VGH 人類肝癌細胞血管新生之影響

Effects of Ginkgo biloba extract and saikosaponin a on angiogenesis in human HA 22T/VGH cells

黃莉婷(Li-Ting Huang)

指導教授 ： 趙振瑞

臺北醫學大學/公共衛生暨營養學院/保健營養學研究所/碩士(2012年)

https://doi.org/10.6831/TMU.2012.00117

摘要

根據行政院衛生署統計肝癌位居癌症死因之第二位。肝癌細胞周圍富含血管，故肝癌細胞可藉由誘發病理性血管新生來增加其生長與轉移途徑。過去常見之肝癌治療方式，有高復發率與藥物耐受性等問題。因此本研究探討銀杏萃取物(Ginkgo biloba extract, EGb 761) 和/或柴胡皂苷 a (saikosaponin a, SSa) 對肝癌細胞血管新生之抑制作用。本研究以亞裔男性之肝癌細胞株 (HA 22T/VGH) 與人類血管內皮細胞株 (EA.hy 926) 共同培養為實驗模式，模擬病理性血管新生之情形，給予不同濃度之 EGb 761 (250 、500 μg/ml, G250、G500) 和/或 SSa (5、7.5 μg/ml, S5、S7.5)，探討對於病理性血管新生之影響。結果顯示單獨給予 EGb 761 與 SSa 組，以及合併給予 EGb 761 與 SSa 組，皆有顯著抑制 EA. hy 926 細胞 invasion 之情形。 EGb 761 與 SSa 對於調控血管新生因子- VEGF 、 MMP-2 ，則具有降低其分泌之作用。推測可能透過降低 VEGF 與 MMP-2 之分泌，來抑制 EA. hy 926 細胞 invasion 。加乘效果經公式計算後，當 IF/IE > 1 時具有加乘效果，合併給予 EGb 761 與 SSa 組， 顯示 MMP-9 之分泌具有加乘效果，而 VEGF 、 MMP-2、 TIMP-1 、 TIMP -2 及EA. hy 926 細胞 invasion ，則不具加乘效果。

關鍵字

肝癌、銀杏萃取物、柴胡皂苷a 、血管新生

並列摘要

Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer death in Taiwan. There were many blood vesssels around HCC, which induced pathological angiogenesis to increase its growths and provide pathways of metastasis. High recurrence rate and drug intolerance have existed in traditional therapy for HCC. This study investigated the effects of EGb 761 and SSa on angiogenesis in human HA 22T/VGH cells. HCC cell line (HA 22T/VGH) and human vascular endothelial cell line (EA.hy 926) were co-cultured with different concentrations of EGb 761 (250, 500 μg / ml G250, G500) and SSa (5,7.5 μg / ml, S5, S7.5) to simulate pathological angiogenesi. Cell invasion of EA.hy 926 was significantly inhibited by EGb 761 or SSa and combined treatment. The secretion of VEGF and MMP-2, proangiogenic factors, tended to be suppressed by the addition of EGb 761 and SSa. Furthermore, EGb 761 and SSa decreased the secretion of VEGF and MMP-2 to inhibit cell invasion of EA.hy 926. After calculation of IF/IE ratio which indicates a synergistic effect as the ratio above 1.0, the combination of EGb 761 and SSa had a synergistic effect on secretion of MMP-9, but not on secretion of VEGF, MMP-2, TIMP-1 and -2 as well as cell invasion of EA. hy 926.

並列關鍵字

Hepatocellular carcinoma (HCC), Ginkgo biloba extract (EGb 761), Saikosaponin a (SSa), angiogenesis

參考文獻

Poon RT, Lau CP, Cheung ST, Yu WC, Fan ST (2003) Quantitative correlation of serum levels and tumor expression of vascular endothelial growth factor in patients with hepatocellular carcinoma. Cancer Res 63:3121–3126.

Ausprunk D, Folkman J (1977) Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 14:53–65.

Bastianetto S, Ramassamy C, Doré S, Christen Y, Poirier J, Quirion R (2000) The ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by β-amyloid. Eur J Neurosci 12:1882-1890.

Bates DO, Harper SJ (2002) Regulation of vascular permeability by vascular endothelial growth factors. Vascul Pharmacol 239:225-237.

Barltop JA, Owen TC, Cory AH, Cory JG (1991) 5- (3-carboxymethoxyphenyl) -2- (4,5-dimenthylthiazoly) -3- (4-sulfophenyl)tetrazolium, inner salt (MTS) and related analogs of 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) reducing to purple water-soluble formazans as cell-viability indicators. Bioorg Med Chem Lett 1: 611-614.