姜黄素联合内皮抑素对小鼠肉瘤生长抑制及血管生成的影响

Effect of Curcumin Combined with Endostatin on Sarcoma Growth Inhibiton and Angiogenesis in Mice

目的探讨姜黄素与内皮抑素联合治疗对小鼠皮下移植肉瘤的生长抑制以及血管生成的影响。方法随机将72只荷瘤小鼠分为对照组、姜黄素组、内皮抑素组和联合治疗组,分别给予相应药物治疗,每天l次,连续给药14d,观察肿瘤生长情况,在荷瘤小鼠处死前从小鼠的尾静脉注射荧光标记物后分离肿瘤组织,计算抑瘤率,观察肿瘤灌注血管荧光标记,计算肿瘤组织的灌注血管平均距离及微血管密度。结果各药物治疗组对肿瘤的生长都有明显的抑制作用,姜黄素组、内皮抑素组、联合治疗组的抑瘤率分别为30.93%,32.33%,61.66%;对照组、姜黄素组、内皮抑素组及联合治疗组的平均灌注血管距离分别为(35.29±6.45),(56.42±9.57),(59.15±10.06),(76.98±11.16)μm,微血管密度分别为(60.35±11.22),(45.23±8.76),(44.77±8.03),(29.62±5.81)个·(400Hp)-1,各药物治疗组与对照组比较差异有统计学意义(P<0.05),联合治疗组与单独用药组比较具有明显的统计学差异(P<0.01);单独用药组之间相比差异无统计学意义。结论姜黄素与内皮抑素治疗小鼠皮下移植肉瘤时都能够抑制肿瘤血管的生成,降低微血管密度,抑制肿瘤的生长,且二者联合治疗的作用效果更佳,明显优于单独用药治疗,表明二者对实体肿瘤的抗血管生成治疗具有协同作用。

OBJECTIVE To investigate the effect of curcumin combined with endostatin on growth inhibition and angiogenesis of subcutaneous transplanted tumor in mice. METHODS Seventy-two sarcoma bearing mice were randomly divided into control group, curcumin group, endostatin group and combined treatment group, gave the corresponding drug treatment, respectively, once a day, 14 d continuous dosing, observed the tumor growth. The mice were sacrificed when fluorescence labeling was injected into the tail vein, then the tumor tissue was isolated. The tumor volumes were measured and the tumor inhibition rate, the tumor perfusion vascular fluorescent tags and microvessel density was calculated. RESULTS Each drug treatment group showed obvious inhibition on tumor growth. The tumor inhibition rates of curcumin group, endostatin group and the combined treatment group were 30.93%, 32.33% and 61.66%, respectively. In the control group, curcumin group, endostatin group and the combined treatment group, the average distance of perfusion vessels was(35.29±6.45),(56.42±9.57),(59.15±10.06),(76.98±11.16)μm, and the microvascular density was(60.35±11.22),(45.23±8.76),(44.77±8.03),(29.62± 5.81) ind·(400 Hp)-1, respectively. There were statistically significant differences between the drug treatment group and the control group(P<0.05), and there were statistically significant differences between the combined treatment group and the single drug treatment group(P<0.01). There was no significant difference between the groups treated alone. CONCLUSION Both curcumin and endostatin can inhibit tumor angiogenesis, decrease microvascular density and inhibit tumor growth when treating subcutaneous sarcoma transplantation in mice. However, the combined treatment has a better effect, which is obviously better than the single drug treatment. It indicates that the combined treatment has a synergistic effect on anti-angiogenic treatment of solid tumors.