OncoTargets and Therapy (May 2020)
Inhibition of Aurora Kinase A by Alisertib Reduces Cell Proliferation and Induces Apoptosis and Autophagy in HuH-6 Human Hepatoblastoma Cells
Abstract
Jingyi Tan,1,* Wenfeng Xu,1,* Lei Lei,1 Hui Liu,1 Hong Wang,2 Xian Cao,1 Man Xu1 1Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Institute of Life Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Man XuDepartment of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaTel +86 131 1011 8908Email [email protected]: Aurora kinase A (AURKA), which belongs to the serine/threonine protein kinase family, has been identified as a key driver of the genesis and progression of diverse tumors. The aim of this study was to determine the clinical significance of AURKA in patients with hepatoblastoma (HB) and the effect of inhibiting AURKA in the HB cell line HuH-6.Methods: The expression of AURKA in HB tissue and adjacent normal liver tissue was detected by immunohistochemistry. Then, statistical analysis was performed to evaluate the association between AURKA expression and the clinicopathological characteristics of HB. The effect of AURKA knockdown on cell viability was assessed by CCK-8 assay. EdU and CCK-8 assays, Western blotting, flow cytometry, and transmission electron microscopy (TEM) were used to examine the effect of alisertib (ALS), a selective AURKA small-molecule inhibitor, on the cell cycle, proliferation, apoptosis, and autophagy in HuH-6 human hepatoblastoma cells.Results: The expression of AURKA was significantly higher in HB tissue than in adjacent normal tissue. Furthermore, high AURKA expression was associated with advanced Children’s Oncology Group (COG) stage and tumor metastasis of HB. In vitro, AURKA knockdown significantly reduced the viability of HuH-6 cells, while ALS treatment significantly suppressed HuH-6 cell proliferation and induced G1-phase cell cycle arrest by reducing cyclin-D1 expression. Moreover, ALS promoted apoptosis and autophagy by decreasing the activity of p38 MAPK in HuH-6 cells.Conclusion: High expression of AURKA is a potential predictor of poor prognosis in HB patients. AURKA knockdown reduced the viability of HuH-6 cells, and ALS treatment inhibited cell proliferation and induced apoptosis and autophagy via the p38 MAPK signaling pathway. Our results suggest that AURKA may be a novel therapeutic target and ALS a potential therapeutic drug for the treatment of HB.Keywords: prognosis, alisertib, proliferation, autophagy, apoptosis
