Furin抑制剂α1-PDX对宫颈癌HeLa细胞生长、转移和成瘤的影响

Effects of α1-PDX, a furin inhibitor, on growth, invasion, and tumorigenicity of cervical cancer HeLa cells

目的研究α1-PDX对宫颈癌细胞株He La细胞生长、转移及成瘤的影响并探讨其机制。方法α1-PDX转染He La细胞,通过MTT细胞增殖实验,Boyden细胞迁移和侵袭实验观察He La细胞的生长,迁移和侵袭能力。采用蛋白印迹法检测细胞Furin及产物膜性Ⅰ型金属蛋白酶(MT1-MMP)蛋白量的变化,荧光酶底物实验检测Furin活性。制作He La细胞致瘤裸鼠模型研究肿瘤体内生长。结果细胞增殖实验结果显示,与对照组相比24 hα1-PDX组He La细胞体外生长抑制18.4%,差异有统计学意义(P<0.01);细胞迁移和侵袭实验结果显示,α1-PDX处理组穿过滤膜和基质胶的He La细胞数量均明显少于对照组(P<0.01);He La/PDX可显著降低Furin的活性和MTI-MMP的蛋白水平。He La/PDX致瘤裸鼠的成瘤机率及皮下肿瘤体积明显小于对照组。结论α1-PDX可有效抑制人宫颈癌He La细胞的生长、转移及成瘤能力,机制可能与降低Furin活性及产物MTI-MMP的表达有关。

Objective To investigate the effects of the furin inhibitor α1- PDX on the growth, invasion, and tumorigenicity of cervical cancer cells and explore the mechanisms. Methods The changes in the growth, migration and invasion of α1- PDXtransfected He La cells were observed using MTT assay, Boyden migration and invasion assay. The protein levels of furin and MT1-MMP were measured using Western blotting and furin activity was detected by enzyme activity assay in the transfected cells. He La cells were seeded subcutaneously in nude mice and the tumor volume changes were recorded. Results Compared with the control cells, α1- PDX- treated cells showed a significant growth inhibition by 18.4% at 24 h（P〈0.01） with obviously lowered migration ability and cell invasiveness（P〈0.01）. Treatment with α1- PDX significantly reduced furin enzyme activity and MTI- MMP protein levels in He La cells. In nude mice, α1- PDX- treated He La cells exhibited a delayed and lowered tumorigenicity with reduced size of the tumors. Conclusion α1-PDX can inhibit the growth, metastasis and tumorigenicity of He La cells, the mechanism of which may involve a decreased furin activity and MTI-MMP expression.