Treg细胞/Th17细胞比例失衡在卵巢癌的生长以及微血管、淋巴管生成中的作用

目的:探讨Treg细胞/Th17细胞比例失衡对移植瘤生长及微血管和淋巴管生成的影响。方法:构建卵巢癌裸鼠皮下和原位移植瘤模型,用磁珠分选人外周血CD3+淋巴细胞,加曲古抑菌素A(TSA)刺激使其Treg/Th17细胞比例失衡,采用流式细胞仪检测Treg/Th17细胞比例。分别将Treg/Th17细胞比例较高和较低的淋巴细胞与人卵巢癌细胞系SKOV3按1∶20比例注射入裸鼠皮下和卵巢包膜下,分别于注射后28天和35天处死称重,观察其对移植瘤生长的影响;免疫组化CD31和LYVE-1染色检测微血管(MVD)和淋巴管(LVD)的表达。结果:Treg高组能促进皮下和原位卵巢癌的生长。皮下模型:注射后第21和28天,Treg高组的肿瘤总荧光强度值均大于Th17高组和对照组;Treg高组的肿瘤重量为(0.60±0.07)g,Th17高组(0.35±0.24)g,对照组(0.25±0.22)g,Treg高组肿瘤重量较Th17高组和对照组重。原位模型:注射后第28天Treg高组肿瘤总荧光强度值均大于其他两组;Treg高组(0.34±0.20)g,Th17高组(0.06±0.03)g,对照组(0.17±0.05)g,Treg高组肿瘤重量比Th17高组重。Treg高组的MVD和LVD表达高于Th17高组和对照组(P0.05)。结论:Treg细胞/Th17细胞比例失衡在卵巢癌裸鼠移植瘤生长中起着重要作用,且Treg高组能影响卵巢癌的生长、微血管和淋巴管的形成。

The effects of Treg/Th17 cells imbalance on proliferation,angiogenesis and lymphangio-genesis of ovarian cancer

Objective：To explore the effects of Treg/Th17 cells Imbalance on prolifera-tion,angiogenesis and lymphangiogenesis of ovarian cancer in nude mice. Methods：Use mag-netic beads to sort CD3＋ lymphocytes in peripheral blood. Use TSA to stimulate CD3＋ lympho-cytes to make Treg / Th17 cells imbalance. Use flow cytometry to detect the rate of Treg cells and Th17 cells. Nude mice were injected with mix of human SKOV3 cells and Treg Group,in which the Treg / Th17 rate was high,by 1 ： 20 in the subcutaneous models and orthotopic models of o-varian cancer. Nude mice were injected with mix of human SKOV3 cells and Th17 Group,in which the Treg / Th17 rate was low. SKOV3 cells were injected as Control Group. Furthermore, the proliferation time,tumor size,LYVE-1 and CD31 expression of ovarian cancer were detec-ted. Results：Treg Group led to an enhancement on tumor proliferation. In the subcutaneous models：Treg Group led to an enhancement on tumor proliferation,compared with Th17 Group and Control Group on the 21th day and 28th day. The tumor weights of three groups when nude mice were sacrificed on the 28th day：Treg Group （0. 60±0. 07）g,Th17 Group （0. 35±0. 24） g,Control Group （0. 25±0. 22）g,in which there were significant difference between Treg Group and the other two group （P〈0. 05）;In the orthotopic models：Treg Group led to an enhance-ment on tumor proliferation,compared with Th17 Group and Control Group on the 28th day. We also found Treg Group showed the highest MVD and LVD, as compared with the other two groups （ P 〈 0. 05）. Conclusion：Treg / Th17 cells imbalance plays important role in ovarian cancer proliferation,angiogenesis and lymphangiogenesis in nude mice.