人参皂苷 Rg3 可减轻原位移植肝癌大鼠模型肝动脉栓塞后肝癌血管内皮生长因子的过度表达。
Ginsenoside Rg3 attenuates hepatoma VEGF overexpression after hepatic artery embolization in an orthotopic transplantation hepatocellular carcinoma rat model.
机构信息
Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, People's Republic of China.
出版信息
Onco Targets Ther. 2014 Oct 21;7:1945-54. doi: 10.2147/OTT.S69830. eCollection 2014.
BACKGROUND
Hypoxia-induced vascular endothelial growth factor (VEGF) upregulation and angiogenesis following treatment of hepatocellular carcinoma (HCC) with transarterial embolization (TAE) or transarterial chemoembolization (TACE) may be mediated by ginsenoside Rg3, an anti-angiogenic saponin extracted from ginseng.
OBJECTIVE
To access the synergistic action of Rg3 and TAE treatment on HCC by VEGF and it's receptor expressions decreasing in a rat model of HCC.
METHODS
An orthotopic transplantation HCC model was established in Buffalo rats. HCC rats were treated with hepatic artery infusions of normal saline or iodized oil (0.1 mL) with or without Rg3 (1 mg/kg) (each n=15 in control, Rg3, TAE, and TAE + Rg3 groups). At 1, 2, 4, and 8 weeks, performance status (body weight), tumor progression (longest tumor diameter), metastasis rate, microvessel density (MVD), and overall survival rate were assessed. Additionally, cluster of differentiation 31 (CD31), VEGF, VEGF receptor 2 (VEGF-R2) and VEGF-R2 phosphorylation levels were assessed by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blot.
RESULTS
Combined Rg3 and TAE treatment reduced tumor progression, body weight loss, angiogenesis, and metastasis rate, and led to better overall survival in the HCC rat model. ELISA results showing VEGF expression in the control, Rg3, TAE, and TAE + Rg3 groups at 4 weeks following treatment were 132.6±2.38, 37.9±0.8, 87.4±0.7, and 45.3±0.4 pg/mL, respectively. Combined Rg3 and TAE reduced the protein expression of CD31 and VEGF-R2 phosphorylation, compared with those in the TAE group at 4 weeks of treatment.
CONCLUSION
Combined Rg3 and TAE treatment limited metastasis and promoted survival by downregulating VEGF overexpression in HCC tumors. Thus, this treatment may have potential clinical implications for HCC patients undergoing TAE or TACE.
背景
经肝动脉栓塞术（TAE）或肝动脉化疗栓塞术（TACE）治疗肝细胞癌（HCC）后，缺氧诱导的血管内皮生长因子（VEGF）上调和血管生成可能由人参中的抗血管生成皂苷人参皂苷 Rg3 介导。
目的
通过降低 HCC 大鼠模型中 VEGF 及其受体的表达，评估 Rg3 与 TAE 联合治疗对 HCC 的协同作用。
方法
建立 Buffalo 大鼠原位移植 HCC 模型。HCC 大鼠分别接受肝动脉输注生理盐水或碘化油（0.1 mL），或同时输注 Rg3（1 mg/kg）（对照组、Rg3 组、TAE 组和 TAE+Rg3 组每组 15 只）。在 1、2、4 和 8 周时，评估行为状态（体重）、肿瘤进展（最长肿瘤直径）、转移率、微血管密度（MVD）和总生存率。此外，通过免疫组织化学、酶联免疫吸附测定（ELISA）和 Western blot 评估分化群 31（CD31）、VEGF、VEGF 受体 2（VEGF-R2）和 VEGF-R2 磷酸化水平。
结果
Rg3 与 TAE 联合治疗可降低 HCC 大鼠模型的肿瘤进展、体重减轻、血管生成和转移率，提高总体生存率。ELISA 结果显示，治疗后 4 周时，对照组、Rg3 组、TAE 组和 TAE+Rg3 组的 VEGF 表达分别为 132.6±2.38、37.9±0.8、87.4±0.7 和 45.3±0.4 pg/mL。与 TAE 组相比，Rg3 与 TAE 联合治疗可降低 CD31 蛋白表达和 VEGF-R2 磷酸化水平。
结论
Rg3 与 TAE 联合治疗通过下调 HCC 肿瘤中 VEGF 的过表达，限制转移并促进生存。因此，这种治疗方法可能对接受 TAE 或 TACE 治疗的 HCC 患者具有潜在的临床意义。
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