Silibinin Inhibits Proliferation and Migration of Human Hepatic Stellate LX-2 Cells

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• 作者：Devaraj Ezhilarasan^* ; Jonathan Evraerts^* ; Sid Brice^&dagger ; ; Pedro Buc-Calderon^&Dagger ; ; Sivanesan Karthikeyan^§ ; ; Etienne Sokal^* ; Mustapha Najimi^* ; ^{mustapha.najimi@uclouvain.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AKR1C1 ; aldo-keto reductase family 1 ; member C1 ; ARE ; antioxidant responsive element ; CDKI ; cyclin dependent kinase inhibitor ; CYP450 ; cytochrome P450 ; DMSO ; dimethylsulphoxide ; DMEM ; Dulbecco's modified Eagle's medium ; ECM ; extracellular matrix ; FBS ; fetal bovine serum ; GAPDH ; glyceraldehyde 3-phosphate dehydrogenase ; HMOX1 ; heme oxygenase (decycling) 1 ; HSCs ; hepatic stellate cells ; NQO1 ; NAD(P)H dehydrogenase ; quinone 1 ; Nrf-2 ; nuclear respiratory factor ; PPIA ; peptidylprolyl isomerase A ; PPA
• 刊名：Journal of Clinical and Experimental Hepatology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：6
• 期：3
• 页码：167-174
• 全文大小：1197 K

文摘

Proliferation of hepatic stellate cells (HSCs) play pivotal role in the progression of hepatic fibrosis consequent to chronic liver injury. Silibinin (SBN), a flavonoid compound, has shown to possess cell cycle arresting potential against many actively proliferating cancers cell lines. The objective of this study was to evaluate the anti-proliferative and cell cycle arresting properties of SBN in rapidly proliferating human hepatic stellate LX-2 cell line.

Methods

LX-2 cells were fed with culture medium supplemented with different concentrations of SBN (10, 50 and 100 μM). After 24 and 96 h of treatment, total cell number was determined by counting. Cytotoxicity was evaluated by trypan blue dye exclusion test. The expression profile of cMyc and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expressions was evaluated by Western blotting. Oxidative stress marker genes profile was quantified using qPCR. The migratory response of HSCs was observed by scrape wound healing assay.

Results

SBN treatments significantly inhibit the LX-2 cell proliferation (without affecting its viability) in dose dependent manner. This treatment also retards the migration of LX-2 cells toward injured area. In Western blotting studies SBN treatment up regulated the protein expressions of PPAR-γ and inhibited cMyc.

Conclusion

The present study shows that SBN retards the proliferation, activation and migration of LX-2 cells without inducing cytotoxicity and oxidative stress. The profound effects could be due to cell cycle arresting potential of SBN.