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目的探讨奥沙利铂(L-OHP)联合热疗在体内外对血管生成的抑制作用。方法采用四甲基偶氮唑盐(MTY)法观察L-OHP联合热疗对人脐静脉内皮细胞(HUVEC)和人结肠癌LOVO细胞增殖的影响;采用transwell实验观察L-OHP联合热疗对HUVEC迁移的影响;采用鸡胚绒毛尿囊膜(CAM)模型观察L-OHP对CAM新生血管的抑制作用。结果0.5～16μs/ml L-OHP均具有抑制HUVEC增殖的作用,细胞存活率为80.1%～42.5%,其增殖速度与L-OHP浓度呈负相关(r=-0.943, P=0.005);在此浓度范围内,L-OHP对LOVO细胞增殖的抑制明显低于对HUVEC的抑制。0.5、1和16μg/ml L-OHP与热疗对HUVEC增殖的抑制具有协同作用,2、4和8μg/ml L-OHP与热疗具有相加作用。0.25～2μg/ml L-OHP具有抑制HUVEC迁移的作用,细胞迁移抑制率为18.7%～53.0%。1、4μg/ml L-OHP对CAM新生血管具有明显的抑制作用,抑制率分别为70.0%和100.0%。结论小剂量L-OHP在体内外具有抑制血管生成的作用,联合热疗对抑制HUVEC增殖具有协同或相加效应。
Objective To investigate the inhibitory effect of oxaliplatin (L-OHP) combined with hyperthermia on angiogenesis in vitro and in vivo. Methods The effects of L-OHP combined with hyperthermia on the proliferation of human umbilical vein endothelial cells (HUVECs) and human colon cancer LOVO cells were observed by MTT assay. The effects of L-OHP combined with hyperthermia HUVEC migration. Chick embryo chorioallantoic membrane (CAM) model was used to observe the inhibitory effect of L-OHP on CAM neovascularization. Results The proliferation of HUVEC was inhibited by 0.5 ~ 16μs / ml L-OHP. The cell survival rate was 80.1% -42.5%. The proliferation rate was negatively correlated with the concentration of L-OHP (r = -0.943, P = 0.005) In this concentration range, the inhibition of LOVO cell proliferation by L-OHP was significantly lower than that of HUVEC. 0.5, 1 and 16μg / ml L-OHP and hyperthermia had synergistic effect on the inhibition of HUVEC proliferation, and 2,4 and 8μg / ml L-OHP had an additive effect with hyperthermia. 0.25 ~ 2μg / ml L-OHP inhibited the migration of HUVEC, the cell migration inhibition rate was 18.7% ~ 53.0%. 1,4μg / ml L-OHP on CAM neovascularization has a significant inhibitory effect, the inhibition rates were 70.0% and 100.0%. Conclusion Low-dose L-OHP can inhibit angiogenesis both in vitro and in vivo. Combined hyperthermia has a synergistic or additive effect on the inhibition of HUVEC proliferation.