红景天提取物对Lewis肺癌小鼠移植瘤中CD4^+CD25^+Treg的抑制作用

Inhibitory effect of sachalin rhodiola rhizome extract on CD4^+CD25^+ regulatory T cells in xenograft tumors of Lewis lung cancer bearing mice

目的:观察红景天提取物(sachalin rhodiola rhizome extract,SRR)对Lewis肺癌小鼠移植瘤中CD4+CD25+调节性T细胞(regulatory T cell,Treg)的抑制作用,初步探讨其抑制肿瘤生长的机制。方法:建立小鼠Lewis肺癌移植瘤模型,随机分为3组:SRR组,紫杉醇(paclitaxel,PTX)阳性对照组和PBS组,记录各组小鼠移植瘤体积变化,计算抑瘤率并观察小鼠生存期。流式细胞术检测移植瘤组织中CD4+CD25+Foxp3+Treg的比例,荧光定量PCR检测移植瘤组织中Foxp3和TGF-βmRNA的表达水平。结果:在建模第20天,SRR组小鼠移植瘤体积明显小于PBS组[(719.6±2.4)vs(1030.5±3.1)mm3,P<0.05],但与阳性对照PTX组无显著差异(P>0.05)。SRR组小鼠生存期较PBS组显著延长[(36.0±1.0)vs(22.0±2.0)d,P<0.01],而与PTX组无显著差异(P>0.05)。SRR治疗组小鼠移植瘤组织中CD4+CD25+Foxp3+Treg占CD4+T细胞的比例显著低于PBS组[(8.5±0.3)%vs(11.2±0.2)%,P<0.01],但与PTX组无显著差异(P>0.05)。SRR组小鼠移植瘤组织中Foxp3 mRNA[(1.2±0.2)vs(2.1±0.2),P<0.05]、TGF-βmRNA[(1.2±0.1)vs(2.1±0.2),P<0.05]表达均明显低于PBS组,而与PTX组无显著差异(P>0.05)。结论:SRR可能通过下调肿瘤组织中CD4+CD25+Treg比例、Foxp3和TGF-βmRNA的表达,增强机体的抗肿瘤免疫应答。

Objective：To observe the inhibitory effect of sachalin rhodiola rhizome extract （SRR） on regulatory T cells （Tregs） in xenograft tumors of Lewis lung cancer bearing mice and primarily discuss its mechanism of suppressing tumor growth. Methods： Lewis lung cancer-bearing mice were established and randomly divided into 3 groups： SRR group, pa- clitaxel （PTX） positive control group and PBS group. The changes of tumor volume were recorded in different groups, tumor inhibition rates were calculated and the survival time of Lewis-bearing mice was observed. The proportion of CD4 ^＋ CD25 ^＋ Foxp3 ^＋ Tregs in the xenograft tumor tissues was detected by flow cytometry. The mRNA expression levels of Foxp3 and TGF-β in the tumor tissues were detected by real-time PCR. Results ： On day 20 after the establishment of the Lewis- bearing mouse model, the tumor volume of mice in the SRR group was significantly smaller than that in the PBS group （ [ 719.6 ± 2.4 ] vs [ 1 030.5 ± 3.1 ] mm^3, P 〈 O. 05 ）, and showed no significant difference with the IYTX positive con- trol group （P 〉 0.05 ）. Compared with the PBS group, the survival time of mice in the SRR group was significantly pro- longed （ [ 36.0 ± 1.0 ] vs [ 22.0 ± 2.0 ] d, P 〈 0.05 ）, and showed no significant difference with the PTX group （ P 〉 0. 05 ）. The proportion of CD4 ^＋ CD25 ^＋ Foxp3 ^＋ Tregs in CD4 ^＋ T cells of the tumor tissues in the SRR group was signifi- cantly lower than that of the PBS group （ [ 8.5 ± 0.3 ] % vs [ 11.2 ± 0.2 ] %, P 〈 0.01 ）, and no significant differencewas observed between the SRR group and the PTX group （P 〉 0.05 ）. The mRNA expressions of Foxp3 （ [ 1.2 ± 0.2 ] vs [ 2. 1 ± 0. 2 ], P 〈 0. 05 ） and TGF-β （ [ 1.2 ± O. 2 ] vs [ 2.1 ±0. 2 ], P 〈 0. 05 ） in SRR group were significantly lower than that in the PBS group, and no significant difference was observed between the SRR group and the PTX group （P 〉 0. 05 ）. Conclusion： SRR may enhance the antitumor immune response by down-regulating the proportion of CD4 ^＋ CD25 ^＋ Tregs and the mRNA expressions of Foxp3 and TGF-15 in the tumor tissues.