AMD3100对Lewis肺癌进展及荷瘤鼠脾脏髓源抑制性细胞积聚的影响

Effects of AMD3100 on progression of Lewis lung carcinoma and accumulation of myeloid derived suppressor cells in tumor-bearing mice's spleen

目的观察趋化因子受体CXCR4拮抗剂AMD3100对Lewis肺癌进展及荷瘤鼠脾脏髓源抑制性细胞(myeloid derived suppressor cells,MDSCs)积聚的影响。方法 60只荷Lewis肺癌C57BL/6小鼠分为2组:PBS组(腹腔只注射PBS液,0.2ml/只)、AMD3100组[腹腔注射溶解有2mg/(kg·d)AMD3100的PBS液,0.2ml/只,1次/d,共26d],每组30只。隔日测2组小鼠体质量,记录成瘤时间。26d随机处死2组荷瘤鼠各15只,剥离瘤体称量,观察肺转移灶数目,用免疫组化法计数瘤组织微血管密度(microvessel density,MVD),流式细胞仪测小鼠脾脏MDSCs比例;统计2组剩余小鼠自然生存天数。结果 PBS组、AMD3100组小鼠Lewis肺癌成瘤时间分别为(8.03±1.47)、(9.97±1.50)d,接种瘤细胞后26d瘤质量分别为(3.54±0.93)、(2.09±0.66)g,MVD值分别为(41.40±6.44)、(32.47±5.33)个/HP,肺癌肺转移灶数目分别为(18.27±9.78)、(7.40±5.83)个/只,MDSCs比例分别为(19.57±3.59)%、(31.42±5.04)%,中位生存时间分别是第29、34天,2组各项指标比较差异均有统计学意义(P<0.01)。结论 AMD3100可延缓Lewis肺癌进展,但可能对荷Lewis肺癌小鼠免疫产生一定的抑制作用。

Objective To investigate the effects of AMD3100,a specific antagonist of chemokine receptor-4,on the progression of Lewis lung carcinoma and the accumulation of myeloid derived suppressor cells （MDSCs） in tumor-bearing mice＇s spleen. Methods Sixty C57BL/6 mice,inoculated subcutaneously Lewis lung carcinoma cell line LLC,were separated into 2 groups （n=30）,the PBS and AMD3100 group. The mice in the 2 groups were intraperitoneally injected with 0.2 ml PBS solution or 0.2 ml PBS solution dissolved with AMD3100 [2 mg/（kg·d）] separately. All the mice were injected once per day,and the injection was lasted for 26 d. The mice＇s weight were measured every other day and the time of oncogenesis was recorded. In 26 d later,15 mice in every group were randomly sacrificed to count the number of pulmonary metastatic nodules and the weight of Lewis lung carcinoma. Flow cytometry and immunohistochemistry were used to detect the percentage of MDSCs in mice＇s spleen and the tumor＇s microvessel density （MVD） separately. Survival time of the remaining mice in the 2 groups were recorded. Results The time of oncogenesis in PBS and AMD3100 group were（8.03±1.47） and （9.97±1.50） d separately. The tumor＇s weight,MVD,number of pulmonary metastatic nodules and percentage of MDSCs in PBS group were （3.54±0.93）g,（41.40±6.44）/HP,（18.27±9.78） nodules /animal,and （19.57±3.59）% respectively. But,in AMD3100 group,these indexes were （2.09±0.66）g,（32.47±5.33）/HP,（7.40±5.83） nodules /animal,and （31.42±5.04）% separately. The median survival time in PBS and AMD3100 group was 29 and 34 d separately. All the indexes between the 2 groups were significant（P0.01）. Conclusion AMD3100 inhibits the progression of Lewis lung carcinoma,but it may also have some negative impacts on the immune of the mice bearing Lewis lung carcinoma.