OncoTargets and Therapy (Feb 2020)
Inhibition of cyclinB1 Suppressed the Proliferation, Invasion, and Epithelial Mesenchymal Transition of Hepatocellular Carcinoma Cells and Enhanced the Sensitivity to TRAIL-Induced Apoptosis
Abstract
Shuai Lv, Hanbing Ning, Yingxia Li, Jingyun Wang, Qiaoyu Jia, Hongtao Wen Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450018, Henan Province, People’s Republic of ChinaCorrespondence: Shuai Lv; Hongtao WenDepartment of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou 450018, Henan Province, People’s Republic of ChinaTel +86-371-6627-1112Email [email protected]; [email protected]: CyclinB1 is highly expressed in various tumor tissues and plays an important role in tumor progression. However, its role in hepatocellular carcinoma (HCC) remains unclear. Therefore, the aim of this study was to explore the role of cyclinB1 in the development and progression of HCC.Methods: The expression of cyclinB1 was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database, and detected in HCC tissues and HCC cell lines through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. CyclinB1-short hairpin RNA (Sh-cyclinB1) was transfected into HCC cells to knockdown cyclinB1, and the effect of cyclinB1 knockdown on HCC was examined via the MTT assay, colony formation assay, wound healing assay, scratch assay, cell cycle analysis in vitro, and xenograft model in nude mice. In addition, the role of cyclinB1 on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis was measured using flow cytometry and Western blotting.Results: The GEPIA database analysis showed that cyclinB1 was highly expressed in HCC tissues. The results of qRT-PCR and Western blotting proved that the expression of cyclinB1 was significantly increased in HCC tissues and cell lines. The data of the MTT assay, colony formation assay, and cell cycle analysis indicated that cyclinB1 knockdown inhibited the proliferation of HCC cells. In addition, cell migration, invasion, and epithelial mesenchymal transition were also impaired by cyclinB1 knockdown. Furthermore, the xenograft model in nude mice demonstrated that inhibition of cyclinB1 suppressed tumor growth and metastasis in vivo. Finally, the results of flow cytometry and Western blotting indicated that inhibition of cyclinB1 enhanced the sensitivity of HCC cells to TRAIL-induced apoptosis.Conclusion: Overall, these data provide reasonable evidence that cyclinB1 may serve as a proto-oncogene during the progression of HCC.Keywords: cyclinB1, proliferation, hepatocellular carcinoma, TRAIL
