索拉非尼联合肝素抑制血管生成的研究

Anti-angiogenic effect of sorafenib combined with heparin

目的观察并比较索拉非尼、肝素单药及联合应用对血管生成的抑制作用。方法60只8日龄鸡胚随机分为6组(n=10):对照组(给予高糖DMEM)、索拉非尼组(给予索拉非尼20nmol)、普通肝素组(给予普通肝素5U)、低分子肝素组(给予低分子肝素5U)、索拉非尼+普通肝素组(给予索拉非尼20nmol和普通肝素5U)、索拉非尼+低分子肝素组(给予索拉非尼20nmol和低分子肝素5U),分别加药并继续孵育,加药72h后观察鸡胚尿囊膜的血管生长的情况。结果单药组的血管数目(索拉非尼组:8.9±1.9条,普通肝素组:7.6±2.3条,低分子肝素组:6.9±1.3条)较对照组(26.8±2.3条)明显减少(P<0.05),联合用药组(索拉非尼+普通肝素组:4.5±1.5条,索拉非尼+低分子肝素组:4.1±1.6条)较单药组血管数明显减少(P<0.05)。结论索拉非尼、普通肝素、低分子肝素均有抗血管生成的作用,联合使用可以其作用进一步增强。

Objective To observe and compare the anti-angiogenic effect of sorafenib, unfractionated heparin（UFH）and low molecular weight heparin （LMWH）, singly used or in combination, with chick chorioallantoic membrane assay. Methods Sixty 8d-developed chick embryos were randomly divided into 6 groups （10 each）： control group, sorafenib group, UFH group, LMWH group, sorafenib＋UFH group, and sorafenib＋LMWH group. Drugs were given respectively and incubation continued. The dosage of drugs for each embryo was 20 nmol of sorafenib, 5U of UFH and 5U of LMWH, respectively, and H-DMEM was applied to the embryo in control group in the same volume （2μl）. After continuing incubation for another 72h, the anti-angiogenic effect in each group was observed and the vascular number in the chick chorioallantoic membrane was counted. Results Vascular number in single drug groups （sorafenib group： 8.9±1.9; UFH group： 7.6±2.3; LMWH group： 6.9±1.3） was significantly smaller than that in the control group （26.8±2.3, P〈0.05）. It was also found that vascular number in the combined drug groups （sorafenib＋UFH group： 4.5±1.5; sorafenib＋LMWH group： 4.1±1.6）was significantly smaller than that in the single drug groups （P〈0.05）. Conclusions Sorafenib, UFH and LMWH, when singly used, certainly has the anti-angiogenesis effect, and the effect may be enhanced when used in combination. The results suggests that different targeted drugs used in combination may be able to give better effect in cancer treatment.