Celecoxib derivative OSU-03012 inhibits the proliferation and activation of hepatic stellate cells by inducing cell senescence

Zhang,Jun; Wang,Miao; Zhang,Zuowei; Luo,Zhongguang; Liu,Fei; Liu,Jie

doi:10.3892/mmr.2014.3048

April-2015 Volume 11 Issue 4

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April-2015 Volume 11 Issue 4

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Article

Celecoxib derivative OSU-03012 inhibits the proliferation and activation of hepatic stellate cells by inducing cell senescence

Authors:
- Jun Zhang
- Miao Wang
- Zuowei Zhang
- Zhongguang Luo
- Fei Liu
- Jie Liu
View Affiliations / Copyright

Affiliations: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Gastroenterology, Shanghai East Hospital, Shanghai Tongji University School of Medicine, Shanghai 200120, P.R. China
Pages: 3021-3026
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Published online on: December 4, 2014

https://doi.org/10.3892/mmr.2014.3048
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Abstract

Liver fibrosis may lead to portal hypertension, liver failure or hepatocellular carcinoma, and predominantly results from the proliferation and activation of hepatic stellate cells. OSU‑03012, a non‑cyclooxygenase‑inhibiting celecoxib derivative, has been previously demonstrated to promote apoptosis in certain cell types, however, its function in hepatic fibrosis remains unclear. In the current study, the inhibitory effect of OSU‑03012 on the proliferation of the LX2 human hepatic stellate cell line was evaluated by cell counting kit‑8 assay. Reverse transcription‑quantitative polymerase chain reaction was performed in order to examine the expression of α‑smooth muscle actin and type I collagen, which are representative of LX2 cell activation. The senescence of LX2 cells was measured by senescence‑associated β‑galactosidase staining, and the cell cycle and apoptosis levels were assessed by flow cytometry. The impact of senescence‑associated signaling on protein expression was assessed by western blot analysis. OSU‑03012 was observed to inhibit cell proliferation and prevent the secretion of profibrotic factors in LX2 cells in a dose‑dependent manner. Furthermore, the results demonstrated that OSU‑03012 inhibited the proliferation and activation of LX2 via the induction of cell senescence at the G1 phase, rather than via cell apoptosis. The induction of senescence may be via the upregulation of p16, p21 and p27. In conclusion, the current study provided insight into the pharmacological mechanisms of OSU‑03012 in preventing the proliferation and activation of hepatic stellate cells through cell senescence. The current study supports the theory that OSU‑03012 is a novel agent for potential use against liver fibrosis.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Celecoxib derivative OSU-03012 inhibits the proliferation and activation of hepatic stellate cells by inducing cell senescence

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