Basic study on Aurora-B expression in cervical cancer and targeted inhibitor ZM447439 enhances paclitaxel anti-tumor activity in cervical cancer

刘国燕; 李君; 李力; 郭祥翠

doi:10.3969/j.issn.1007-3969.2014.07.013

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Basic study on Aurora-B expression in cervical cancer and targeted inhibitor ZM447439 enhances paclitaxel anti-tumor activity in cervical cancer

更新时间：2025-12-31

- Basic study on Aurora-B expression in cervical cancer and targeted inhibitor ZM447439 enhances paclitaxel anti-tumor activity in cervical cancer
- China Oncology Vol. 24, Issue 7, Pages: 545-549(2014)
- 作者机构：
  
  河南省新乡市中心医院妇科妇瘤科,河南,新乡,453000
- 作者简介：
- 基金信息：
- DOI：10.3969/j.issn.1007-3969.2014.07.013
  CLC：
- Published Online：29 July 2014，
  
  Published：29 July 2014
- 稿件说明：
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刘国燕,李君,李力,郭祥翠. Aurora-B在宫颈癌组织中的表达与其靶向抑制剂ZM447439增强紫杉醇化疗作用的基础研究[J]. 中国癌症杂志, 2014, 24(7): 545-549.

刘国燕, 李君, 李力, et al. Basic study on Aurora-B expression in cervical cancer and targeted inhibitor ZM447439 enhances paclitaxel anti-tumor activity in cervical cancer[J]. China Oncology, 2014, 24(7): 545-549.
刘国燕,李君,李力,郭祥翠. Aurora-B在宫颈癌组织中的表达与其靶向抑制剂ZM447439增强紫杉醇化疗作用的基础研究[J]. 中国癌症杂志, 2014, 24(7): 545-549. DOI： 10.3969/j.issn.1007-3969.2014.07.013.

刘国燕, 李君, 李力, et al. Basic study on Aurora-B expression in cervical cancer and targeted inhibitor ZM447439 enhances paclitaxel anti-tumor activity in cervical cancer[J]. China Oncology, 2014, 24(7): 545-549. DOI： 10.3969/j.issn.1007-3969.2014.07.013.

摘要

背景与目的：Aurora激酶是调节细胞有丝分裂过程的重要激酶，其在众多肿瘤中呈过度表达，该激酶也就成为新的肿瘤治疗靶点之一。本研究旨在探讨Aurora-B蛋白在宫颈癌中表达及其与宫颈癌临床病理参数的相关性，同时研究Aurora-B靶向抑制剂增强紫杉醇对宫颈癌细胞株SiHa化疗的作用。方法：应用免疫组化法分析70例宫颈癌、46例CINⅡ和21例正常宫颈病理切片。应用MTT法检测了ZM447439、紫杉醇对宫颈癌细胞株的增殖抑制试验。并且通过Western blot分析了SiHa细胞在ZM447439处理后凋亡相关蛋白表达。结果：发现宫颈癌中Aurora-B蛋白高表达(50/70，71.43％)，在鳞癌中高表达(42/50，84%)，并且与细胞分化程度相关(P=0.000 3)。ZM447439作用于SiHa细胞株后有明确的随时间和剂量相关的增殖抑制，并且ZM447439可以对紫杉醇有明确的化疗协同作用(Q1.15)。经Western blot证实ZM447439通过升高P53水平促进SiHa细胞凋亡。结论：宫颈癌中Aurora-B蛋白高表达，靶向Aurora-B的ZM447439可以协同增强紫杉醇对宫颈细胞株抑制作用。

Abstract

Background and purpose: Aurora kinases

frequently detected to be over-expressed in some human tumors

regulate many essential events during tumor cell mitosis progression and have been regarded as potentially important targets for cancer therapy. This study was designed to detect Aurora-B expression in cervical carcinoma

explore the relation Aurora-B expression and clinicopathologic feature. So

Aurora-B kinase inhibition ZM447439 was used to investigate the effect of ZM447439 on SiHa cell line and the synergy effect with paclitaxel. Methods: Detected Aurora-B protein in cervical carcinoma(70 patients)

CINⅡ(46 patients) and normal cervix(21patients) by immunohistochemistry. The inhibitory effects of ZM447439 and paclitaxel in SiHa cell line were investigated by MTT based assay

The expression of apoptosis associated protein was measured by Western blot.Results: The rate of Aurora-B expression is 71.43% in cervical cancer

with no significant correlation to clinical stage

age

lymph node metastasis

vascular invasion (P0.05). Aurora-A protein expression has significant correlation to pathological type and grade(P0.05). Enhanced antiproliferative effects were found when SiHa cells were cultured with ZM447439. Synergic effect of ZM447439 combined with paclitaxel was found in SiHa cell line(Q1.15). The level of P53 was increased significantly through ZM447439 treatments with Western blot. Conclusion: Our data provides strong evidence that high expression of Aurora-B in cervical cancer. The targeted Aurora-B inhibitors

ZM447439

can enhance paclitaxel anti-tumor activity in cervical cancer.

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