State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Int J Oncol. 2012 Dec;41(6):2139-49. doi: 10.3892/ijo.2012.1633. Epub 2012 Sep 20.
Aurora kinases have been shown to be involved in the regulation of the cell cycle and are related to tumor progression. This suggests the possibility that they can serve as new anticancer targets for tumor treatment. However, the important roles that Aurora kinases and their signaling pathway play in renal cell carcinoma (RCC) are not fully understood and addressed to date. In this study, we aimed to address these questions. We observed that downregulation of Aurora kinases induced by AurA miRNA, AurB miRNA or VX680 could inhibit proliferation and metastasis, induce G2/M phase arrest in clear cell renal cell carcinoma cells and exert antitumor activity in an SN12C xenograft model. We also show that either silencing of Aurora kinases or treating the cells with VX680 could downregulate the expression of cdc25c and cyclin B/cdc2, upregulate the expression of p-cdc2 (Tyr15) via blocking the activity of ERK. All these changes may contribute to inhibition of proliferation, metastasis and G2/M arrest in ccRCC. In summary, we proved that both Aurora kinases A and B are key elements of tumor growth regulation, and inhibition of Aurora kinases may contribute to blocking ccRCC progression. We conclude that Aurora kinases could be potential therapeutic targets in the management of renal cell carcinoma.
极光激酶已被证明参与细胞周期的调节，与肿瘤的进展有关。这表明它们可能成为肿瘤治疗的新的抗癌靶点。然而，极光激酶及其信号通路在肾细胞癌（RCC）中的重要作用尚未得到充分理解和解决。在这项研究中，我们旨在解决这些问题。我们观察到 AurA miRNA、AurB miRNA 或 VX680 下调极光激酶的表达可抑制增殖和转移，诱导透明细胞肾细胞癌细胞的 G2/M 期阻滞，并在 SN12C 异种移植模型中发挥抗肿瘤活性。我们还表明，沉默极光激酶或用 VX680 处理细胞可下调 cdc25c 和 cyclin B/cdc2 的表达，通过阻断 ERK 的活性上调 p-cdc2（Tyr15）的表达。所有这些变化可能有助于抑制 ccRCC 的增殖、转移和 G2/M 期阻滞。总之，我们证明了 Aurora 激酶 A 和 B 都是肿瘤生长调节的关键因素，抑制 Aurora 激酶可能有助于阻断 ccRCC 的进展。我们得出结论，Aurora 激酶可能是肾细胞癌治疗的潜在治疗靶点。
