Sun Jian-Ming, Yang Li-Na, Xu Han, Chang Bin, Wang Hua-Ying, Yang Gong
Cancer Institute, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Gynecological Oncology, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China ; Department of Obstetrics and Gynecology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200062, China.
Cancer Institute, Fudan University Shanghai Cancer Center Shanghai 200032, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai 200032, China.
Am J Cancer Res. 2015 Feb 15;5(3):1133-45. eCollection 2015.
Aurora kinase A (AurA) regulates genomic instability and tumorigenesis in multiple cancer types. Although some studies have reported that Aur A may predict cervical cancer outcomes, its precise function and molecular mechanism in cervical cancer pathogenesis remain unclear. In this study, by overexpression or silencing of Aur A in cervical cancer cell lines, we found that overexpression of Aur A promoted cell proliferation through G1/S cell cycle transition and anti-apoptosis, xenograft tumor growth and chemoresistance to Taxol. We further found that inhibition of Aur A with its specific inhibitor VX-680 enhanced the antitumor effect of Taxol via inducing apoptosis. Moreover, the clinical analysis from tissue samples demonstrated that Aur A was overexpressed, and the expression of Aur A and pERK1/2 was negatively correlated in cervical cancer tissues. The above results may provide some potential insights in treatment of cervical cancer in clinic.
极光激酶A（AurA）在多种癌症类型中调节基因组不稳定性和肿瘤发生。尽管一些研究报道AurA可能预测宫颈癌的预后，但其在宫颈癌发病机制中的精确功能和分子机制仍不清楚。在本研究中，通过在宫颈癌细胞系中过表达或沉默AurA，我们发现AurA的过表达通过G1/S细胞周期转换和抗凋亡促进细胞增殖、异种移植肿瘤生长以及对紫杉醇的化疗耐药。我们进一步发现，用其特异性抑制剂VX-680抑制AurA可通过诱导凋亡增强紫杉醇的抗肿瘤作用。此外，来自组织样本的临床分析表明，AurA在宫颈癌组织中过表达，且AurA与pERK1/2的表达在宫颈癌组织中呈负相关。上述结果可能为临床治疗宫颈癌提供一些潜在的见解。
