肝癌移植瘤小鼠髓样抑制细胞比例变化及亚砷酸的调节作用  

The Changes in Myeloid Derived Suppressor Cells in Mice with Hepatic Transplanted Tumor and the Regulatory Effects of Arsenious Acid

作　　者：王士勇[1] 张远[1] 杨云锋[1] 杜微丽[1] 张晖[1] 刘飒[1] 张哲[1] 何英[1] 王佳玲[1] 武秀艳[1] 

机构地区：[1]中国医科大学附属第四医院生物治疗科,沈阳市110032

出　　处：《中国肿瘤临床》2010年第4期194-197,共4页Chinese Journal of Clinical Oncology

基　　金：教育部留学回国人员科研启动基金资助(编号:2004-527)~~

摘　　要：目的:探讨髓样抑制细胞(MDSCs)与肿瘤发生、发展的相关性,寻找抑制肿瘤生长的方法。方法:建立H_(22)肝癌细胞昆明鼠皮下移植瘤模型,用共聚焦显微镜观察MDSCs形态;应用流式细胞仪检测外周血及脾脏中MDSCs数量在肿瘤生长过程中的变化趋势;给予As_2O_3药物干预,即随机分为对照组、As_2O_3低剂量组(2mg/kg)、As_2O_3高剂量组(4mg/kg);每周腹腔给药2次,重复上述测量,统计学分析组间差异;体外细胞培养观察As_2O_3对小鼠MDSCs数量的直接影响。结果:皮下接种肿瘤细胞株后,瘤重逐渐增加,第25天增加至5.67g,外周血和脾脏MDSCs比例也逐渐增加,分别达20.46%和9.50%;对瘤重与外周血和脾脏MDSCs比例的变化趋势进行相关性分析,相关系数r值分别为0.95和0.96(t=5.270、5.939,P<0.05),两者明显呈正相关关系。当用As_2O_3药物干预时,外周血低剂量组和高剂量组MDSCs比例在第28天上升至11.31%和10.00%,明显低于阴性对照组(t=3.193、5.486,P<0.05),且高剂量组MDSCs比例明显低于低剂量组(t=3.066,P<0.05);脾脏低剂量组和高剂量组MDSCs比例在第28天上升至10.90%和9.04%,明显低于阴性对照组(t=3.586、5.279,P<0.05),但高、低剂量组间差异无统计学意义(t=1.298,P>0.05)。体外实验中,在加入H_(22)肿瘤腹水上清后,培养液中MDSCs比例于第12天上升至12.67%;加入As_2O_3继续培养,MDSCs的比例于第18天下降至7.44%,分别与其前一时间点比较,差异有统计学意义(P<0.05)。结论:荷H_(22)肝癌细胞小鼠体内MDSCs比例随着肿瘤负荷增大而增加,两者存在正相关性;As_2O_3可以降低MDSCs的比例,缓解肿瘤发生、发展。Objective： To discuss the correlation between myeloid derived suppressor cells （MDSCs） and hepatic trans- planted tumor and to explore new ways to inhibit the development of hepatic cancer. Methods： We established the animal models with H22 hepatic carcinoma cells transplanted to the anterior right limb. Then the MDSCs morphology was observed with confocal microscopy and the proportion of MDSCs in blood and spleen was measured with flow cytometry. The 36 mice were divided into three groups： the control group, the low-dose group （2mg/kg） and the high-dose group （4mg/kg）. Then As203 was injected twice a week to the mice before repeating the aforementioned measures. The direct effects of As2O3 on MDSCs cultured with H22-ascites supernatant was observed. Results： At 25 days after transplantion, the tumor weight was increased to 5.67g, and the proportion of MDSCs in blood and spleen was increased to 20.46% and 9.50%, re- spectively. There was a positive correlation between hepatic transplanted tumor and MDSCs in blood and spleen and the relative factors were 0.95 and 0.96, respectively （t=5.270 and 5.939, P〈0.05）. With the effect of As203, the proportion of MDSCs in blood in low-dose group and high-dose group was 11.31% and 10.00% at 28 days after treatment, lower than that in the control group （t=3.193 and 5.486, P〈0.05）, and there was also a statistical difference between the high-dose group and low-dose group （t=-3.066, P〈0.05）. The proportion of MDSCs in the spleen in low-dose group and high-dose group was 10.90% and 9.04% at 28 days, lower than that in the control group （1=3.586 and 5.279, P〈0.05）, but there was no statistical difference between the high-dose group and low-dose group （t=1.298, P〉0.05）. In vitro, the proportion of MDSCs in nutrient fluid was increased to 12.67% at 12 days after treatment with H22-ascites supernatant, and was decreased to 7.44% at 18 days after treatment with As2O3. Conclusion： The proportion of MDSCs in H22 tumor-bearing mice i

关 键 词：髓样抑制细胞 亚砷酸 肝细胞癌小鼠 

分 类 号：R735.7[医药卫生—肿瘤]