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 (P>0.05). Aurora-A protein expression has significant correlation to pathological type and grade(P<0.05). 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(Q>1.15). 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.

Key words: Cervical carcinoma, Aurora-B, Targeted therapy, Paclitaxel