| چکیده انگلیسی مقاله |
Background: Metastasis of cancer cells is the primary responsible for death in patients with colorectal cancer (CRC). Transforming growth factor-β (TGF-β)-induced matrix metalloproteinases (MMPs) are essential for the metastasis process. Silibinin is a natural compound extracted from the Silybum marianum that exhibits anti-neoplastic activity in cancer cell lines. In this study, we evaluated the effects of silibinin on MMP-2 and MMP-9 induced by TGF-β in human HT-29 CRC cell line and the potential mechanism underlying the effects.
Methods: The present in vitro study was done on the HT-29 cell line. The HT-29 cell line was cultured in RPMI1640 and exposed to TGF- β (5 ng/ml) in the absence and presence of different concentrations of silibinin (10, 25, 50, and 100 μM). The effect of silibinin on HT-29 cell viability was measured with the MTT assay. A real-time polymerase chain reaction (Real-Time PCR) determined the relative mRNA expression of MMP-2 and MMP-9. Western blotting was employed to examine MMP-2 and MMP 9 protein expression and Smad2 phosphorylation.
Results: Silibinin inhibits cell viability of HT-29 cell line at 24 hours in a dose-dependent manner. TGF-β increased the mRNA and protein expression of MMP-2, MMP-9, and phosphorylated Smad2 compared to controls. Pharmacological inhibition with silibinin markedly blocked TGF-β–induced MMP-2 and MMP-9 mRNA and protein expression and Smad2 phosphorylation.
Conclusion: Silibinin decreased the cell viability of HT-29 cancer cells in a dose-dependent manner. Silibinin also inhibited TGF-β-stimulated MMP-2 and MMP-9 expression in HT-29 cells, possibly mediated with the Smad2 signaling pathway. |
| نویسندگان مقاله |
| Zahra Zare
Department of Biology, Farhangian University, Tehran, Iran.
| Tina Nayerpour Dizaj
Department of Medical Biotechnology, Faculty of Modern Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| Armaghan Lohrasbi
Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, UK. AND Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.
| Zakieh Sadat Sheikhalishahi
Department of Physiology, Shahid Sadoghi University of Medical Sciences, Yazd, Iran.
| Amirhooman Asadi
Veterinary Medicine, Faculty of Veterinary Medicine, Karaj Branch, Islamic Azad University, Karaj, Iran.
| Mana Zakeri
Department of Biology, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.
| Fahimeh Hosseinabadi
Biology Department, Faculty of Sciences, Arak University, Arak, Iran.
| Omid Abazari
Department of Clinical Biochemistry, school of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
| Mojtaba Abbasi
Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran. AND Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
| Parisa Khanicheragh
Department of Clinical Biochemistry, Lorestan University of Medical Sciences, Khorramabad, Iran.
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