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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 investigate the correlation between myeloid suppressor cells (MDSCs) and tumorigenesis and development, and to find ways to inhibit tumor growth. Methods: The H22 hepatocarcinoma xenografts in Kunming mice were established. The morphological changes of MDSCs were observed with confocal microscopy. The changes of MDSCs in peripheral blood and spleen were observed by flow cytometry. The effects of As_2O_3 intervention , Which were randomly divided into control group, As2O3 low dose group (2mg / kg), As2O3 high dose group (4mg / kg); intraperitoneal administration twice a week, repeat the above measurements, statistical analysis of differences between groups; in vitro cell culture To observe the direct effect of As_2O_3 on the number of mouse MDSCs. Results: After subcutaneous inoculation of tumor cell lines, the tumor weight increased gradually and increased to 5.67g on the 25th day. The proportion of MDSCs in peripheral blood and spleen increased gradually by 20.46% and 9.50%, respectively. The ratio of MDSCs to tumor weight, peripheral blood and spleen The correlation coefficient r was 0.95 and 0.96 respectively (t = 5.270, 5.939, P <0.05), showing a positive correlation between the two. The percentage of MDSCs in peripheral blood low-dose group and high-dose group increased to 11.31% and 10.00% on day 28 when compared with that of negative control group (t = 3.193, 5.486, P <0.05) The proportion of MDSCs in low-dose group and high-dose group increased to 10.90% and 9.04% on day 28, significantly lower than that in negative control group (t = 3.066, P <0.05) = 3.586,5.279, P <0.05), but there was no significant difference between high and low dose groups (t = 1.298, P> 0.05). In in vitro experiments, the percentage of MDSCs in culture medium increased to 12.67% after adding H_ (22) tumor ascites supernatant, and the proportion of MDSCs decreased to 7.44% on the 18th day after adding As_2O_3, At one time point, the difference was statistically significant (P <0.05). CONCLUSION: The proportion of MDSCs in H22 hepatocarcinoma cells increases with tumor burden, and there is a positive correlation between them. As2O3 can reduce the proportion of MDSCs and alleviate tumorigenesis and development.