TACE联合索拉非尼抗兔VX2肝癌血管生成
Effect of TACE combined with sorafenib on angiogenesis of VX2 liver cancer in rabbits

摘要：目的 利用新西兰兔VX2肝癌模型，探讨经导管动脉化疗栓塞术(TACE)联合索拉非尼治疗肝癌的疗效、抗血管生成的作用机制及联合时机选择。方法 新西兰兔VX2肝癌模型30只，随机分为生理盐水对照组、单TACE组、单索拉非尼组、TACE术前+索拉非尼组、TACE术后+索拉非尼组(各6只)。分别于TACE术前7d、术前1d、术后第3、7和14天通过ELISA法定量测定血清血管内皮生长因子(VEGF)，术后第14天处死所有瘤兔行肿瘤组织微血管密度(MVD)免疫组化染色，同时比较各组肿瘤增长率。结果 与生理盐水对照组比较，单TACE组、TACE术前+索拉非尼组、TACE术后+索拉非尼组术后3d血清VEGF显著升高(P<0.05)，但TACE术前+索拉非尼组VEGF峰值低于单TACE组、TACE术后+索拉非尼组两组(P<0.05)；14d各组VEGF水平差异均有统计学意义(P<0.05)，TACE术前+索拉非尼组VEGF水平最低，单TACE组最高。术后14d TACE术前+索拉非尼组MVD值高于生理盐水对照组和单索拉非尼组，但明显低于单TACE组(P<0.05)。术后14d TACE术前+索拉非尼组肿瘤增长量最小(P<0.05)。结论 TACE联合索拉非尼治疗兔VX2肝癌，可显著抑制肿瘤增长，疗效优于单纯TACE或单纯索拉非尼治疗；TACE术后VEGF水平升高，联用索拉非尼可降低血清VEGF水平，进而使肿瘤微血管密度下降；TACE术前联合索拉非尼抗肿瘤及抗血管生成的效果要优于术后。
ABSTRACT: Objective To investigate the efficacy of antiangiogenesis, mechanism and timing of transcatheter arterial chemoembolization (TACE) combined with sorafenib in treatment of liver cancer in new Zealand rabbits with VX2 liver cancer model. Methods Thirty New Zealand rabbits with VX2 liver cancer were randomly divided into normal saline control group, single TACE group, single sorafenib group, pre-TACE + sorafenib group and post-TACE + sorafenib group (n=6 in each). Serum VEGF was measured by ELISA 7 days before TACE, 1 day before TACE, 3 days after TACE, 7 days after TACE, and 14 days after TACE. All the rabbits were sacrificed 14 days after operation for MVD immunohistochemical staining, and the tumor growth rate of each group was compared. Results Compared with that in normal saline control group, serum VEGF in TACE + sorafenib group, TACE + sorafenib group and TACE + sorafenib group increased significantly (P<0.05), but the peak value of VEGF in TACE + sorafenib group was lower than that in TACE group and TACE + sorafenib group(P<0.05). Fourteen days after TACE, the VEGF level in the group + sorafenib was the lowest and that in the group of one drug alone was the highest (P<0.05). In 14 days after TACE + sorafenib group, MVD value was higher than that in saline control group and sorafenib group, but significantly lower than that of single TACE group(P<0.05). The 14 days after TACE + sorafenib group had the smallest tumor growth(P<0.05). Conclusion TACE combined with sorafenib can significantly inhibit the growth of VX2 liver cancer in rabbits. The effect of TACE combined with sorafenib is better than that of TACE alone or sorafenib alone. However, after TACE the level of VEGF is increased and the level of serum VEGF is decreased by combining sorafenib, which decreases the microvessel density. Moreover, the effect of TACE combined with sorafenib on anti-tumor and anti-angiogenesis is better than that after