As2O3对ACC-2移植瘤血管生成的影响

Effects of arsenic trioxide on ACC - 2 xenografts angiogenesis in nude mice

目的研究三氧化二砷（As2O3）对人腺样囊性癌ACC-2裸鼠移植瘤生长及血管生成的抑制作用，探讨其抗肿瘤的作用机制。方法通过建立ACC-2裸鼠移植瘤模型，将28只荷瘤鼠随机分为4组：阴性对照组（生理盐水即NS）、阳性对照组[5-Fu10mg／（kg·d）]、低剂量组[As2O3．5mg／（kg·d）]、高剂量组[As2O3 5．0mg／（kg·d）]。连续经腹腔注射用药10天。测量肿瘤的体积和重量，采用HE染色光镜观察，免疫组织化学法检测VEGF、MVD的表达并进行统计学分析。结果高、低剂量As2O3组移植瘤的瘤体积、瘤重均低于两对照组（Ns组和5-Fu组），且高剂量As2O3组抑瘤最明显，瘤体积抑制率为52．17％，瘤重抑制率为56．04％（P〈0．01）。在移植瘤表面，与两对照组相比，高、低剂量As2O3组血管密度减小，管径变细。高、低剂量As2O3组抑制移植瘤VEGF的表达、降低MVD值，高剂量As2O3组抑制作用最明显。与两对照组比较以及高、低剂量As2O3组之间比较差异均有统计学意义（P〈0．01）。结论As2O3对人腺样囊性癌ACC-2裸鼠移植瘤及血管生成有明显抑制作用，其作用机制可能为降低VEGF表达及MVD值，此抑制作用与剂量有关。

Objective This study is to investigate the inhibitory effect of Arsenic Trioxide （As2O3 ）on salivary adenoid cystic carcinoma - 2 （ ACC - 2） cell xenografts and angiogenesis in nude mice. Methods The nude mice with ACC -2 cell xenografts were randomly distributed into four groups, control normal saline（NS） ,5 -Fu group[5 -Ful0 mg/（kg d）] ,low- dose group[ As2O3 2.5 mg/（kg d） ] ,and high- dose group[As2O3 5.0 mg/（kg d）]. 0.2 mL NS or drugs were given by intraperitoneal injection for 10 days. Tumor vdume and weight were measured,the microstructure was observed by HE staining,the expression of VEGF and MVD were detected by immunohistochemistry. Results The average tumor volume was significantly smaller and the average tumor weight was significantly lighter in As2O3 groups than in control groups, especially in the high -dose group, the inhibitory rate were 52.17% and 56.04% （ P 〈0.01 ）. Compared with the control group,the MVD of treat- ment group was markedly decreased, the pipe diameters were smaller in treatment group. The expression levels of VEGF and MVD were significantly lower in As2O3 groups than in control group, especially in the high - dose group. Conclusion As2O3 has obviously inhibitory effects on growth of ACC -2 cell xenografts and angiogenesis in nude mice by suppressing the expression of VEGF and MVD. The anticancer effect of As2O3 is related to the As2O3 concentration.