【摘要】 目的探讨三氧化二砷（aresenic trioxide,AS₂O₃）抑制裸鼠荷人子宫内膜癌皮下移植瘤的生长作用机制,研究其不良反应。方法建立裸鼠荷人子宫内膜癌HEC-1-A细胞移植瘤动物模型,随机分为AS₂O₃组（6mg·kg-1·d-1）、顺铂（cisplatin,CDDP）组（3mg·kg-1·d-1）及生理盐水组（对照组）,腹腔连续给药14d,计算瘤体积变化,观察裸鼠一般情况,检测用药后裸鼠的肝肾功能及血常规,采集各脏器称湿质量,肿瘤组织用于病理学分析和免疫组织化学分析。结果 AS₂O₃组和CDDP组抑制肿瘤体积生长的作用与生理盐水组比较差异均有统计学意义（P<0.05）,且AS₂O₃抑瘤作用优于CDDP。用药后AS₂O₃组裸鼠未出现恶病质,除出现白细胞和血小板抑制外,肝肾功能和主要脏器无明显变化,而CDDP组裸鼠出现明显恶病质表现,血象及肝肾功能均受影响。AS₂O₃作用后肿瘤组织的增殖细胞核抗原（Proliferating cell nuclear,PCNA）表达呈下降趋势,p27表达呈上升趋势。结论 AS₂O₃对鼠荷人子宫内膜癌移植瘤的生长有抑制作用,作用强于CDDP,而不良反应弱,其作用机制可能与下调PCNA和上调p27的表达有关。因此,AS₂O₃很有希望成为一种新型的子宫内膜癌治疗药物。更多还原

【Abstract】 Objective To explore the inhibitory mechanism of arsenic troixide（AS₂O₃）on the growth of nude mice bearing human endometrial cancer with subcutaneous transplanted tumor,to research adverse reactions.Methods Human endometrial cancer xenograft models were established in nude mice using HEC-1-A cell,then were divided into three groups as following:AS₂O₃group（6 mg·kg-1·d-1）,cisplatin（CDDP）group（3 mg·kg-1·d-1）,and negative control group using saline.The drugs were given intraperitoneally for 14 d,then the inhibition rate of tumor volume were calculated,the general of nude mice was observed.The change of liver and kidney function,the blood cell counts of nude mice after treatment were measured.Various organs were collected and weighed.The tumor tissues and the organs were acquired for pathological analysis and immunohistochemical analysis.Results As compared with the saline group,the difference on inhibiting growth of tumor volume in AS₂O₃ group and CDDP group were statistically significant（P< 0.05）,and AS₂O₃ had stronger inhibitory effect than CDDP.AS₂O₃ had no effect on body mass,the function of liver and kidney of nude mice,except a light inhibition on WBC and platelet counts after treatment.While there was obvious cachexia in nude mice of CDDP group,and an obvious impact on the blood cells,the function of liver and kidney were found after CDDP treatment.The expression of PCNA in AS₂O₃ group had a declining trend,while the expression of p27 had an upward trend.Conclusion AS₂O₃ could inhibit the growth of human endometrial cancer xenograft in nude mice,which may due to down-regulating the expression of PCNA and up-regulating the expression of the tumor suppressor gene p27.Furthermore,AS₂O₃ has stronger inhibitory effect than CDDP,with lighter adverse reaction.Thus,AS₂O₃ is a new drug for endometrial cancer treatment.更多还原