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Anti-growth Effects of Imatinib and GNF5 via Regulation of Skp2 in Human Hepatocellular Carcinoma Cells
Journal of Cancer Prevention 2018;23:170-5
Published online December 30, 2018
© 2018 Korean Society of Cancer Prevention.

Sung Hyun Kim1,*, Myoung-Ok Kim2,*, and Ki-Rim Kim3

1China-US (Henan) Hormel Cancer Institute, Henan, China, 2Department of Animal Science, College of Ecology and Environment Science, Kyungpook National University, 3Department of Dental Hygiene, College of Science and Technology, Kyungpook National University, Sangju, Korea
Correspondence to: Ki-Rim Kim
Department of Dental Hygiene, College of Science and Technology, Kyungpook National University, 2559 Gyeongsang-daero, Sangju, 37224, Korea
Tel: +82-54-530-1422, Fax: +82-54-530-1429, E-mail:
ORCID: Ki-Rim Kim,
*These authors contributed equally to this work.
Received September 11, 2018; Revised September 21, 2018; Accepted September 27, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Human hepatocellular carcinoma (HCC) is a common liver tumor and the main cause of cancer-related death. Tyrosine kinase inhibitors, such as imatinib and GNF5 which were developed to treat chronic myelogenous leukemia, regulate the progression of various cancers. The aim of this study was to confirm the anti-tumor activity of tyrosine kinase inhibitors through regulation of S-phase kinase-associated protein 2 (Skp2), an important oncogenic factor in various cancer cells, in human hepatocarcinoma SK-HEP1 cells.
Methods: Cell viability and colony formation assays were conducted to evaluate the effects of imatinib, GNF5 and GNF2 on the growth of SK-HEP1 cells. Using immunoblot analysis, we assessed change of the activation of caspases, PARP, Akt, mitogen-activated protein kinases, and Skp2/p27/p21 pathway by imatinib and GNF5 in SK-HEP1 cells. Using sh-Skp2 HCC cells, the role of Skp2 in the effects of imatinib and GNF5 was evaluated.
Results: Imatinib and GNF5 significantly inhibited the growth of SK-HEP1 cells. Treatment of imatinib and GNF5 decreased Skp2 expression and Akt phosphorylation, and increased the expression of p27, p21, and active-caspases in SK-HEP1 cells. In sh-Skp2 HCC cells, cell growth and the expression of Skp2 were inhibited by more than in the mock group treated with imatinib and GNF5.
Conclusions: These results suggest that the anti-growth activity of tyrosine kinase inhibitors may be associated with the regulation of p27/p21 and caspases through Skp2 blockage in HCC cells.
Keywords : Anti-growth activity, Hepatocellular carcinoma, Skp2, Imatinib, GNF5

December 2018, 23 (4)
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