南方医科大学学报 ›› 2015, Vol. 35 ›› Issue (03): 432-.

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Furin抑制剂α1-PDX对宫颈癌HeLa细胞生长、转移和成瘤的影响

石冲,张国彬,韩宝生,杨俊红,刘恒,习瑾昆   

  • 出版日期:2015-03-20 发布日期:2015-03-20

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

  • Online:2015-03-20 Published:2015-03-20

摘要: 目的研究α1-PDX对宫颈癌细胞株HeLa细胞生长、转移及成瘤的影响并探讨其机制。方法α1-PDX转染HeLa细胞,通
过MTT细胞增殖实验,Boyden细胞迁移和侵袭实验观察HeLa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HeLa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 h α1-PDX组HeLa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HeLa细胞数量均明显少于对照组(P<0.01);
HeLa/PDX可显著降低Furin的活性和MTI-MMP的蛋白水平。HeLa/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HeLa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。

Abstract: 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 α
1-PDX-transfected HeLa 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. HeLa 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 HeLa cells. In nude mice, α1-PDX-treated HeLa cells exhibited a delayed and lowered
tumorigenicity with reduced size of the tumors. Conclusion α1-PDX can inhibit the growth, metastasis and tumorigenicity of
HeLa cells, the mechanism of which may involve a decreased furin activity and MTI-MMP expression.