P- 28 ATORVASTATIN SHOWS ANTI-PROMOTOR AND ANTI-NEOANGIOGENIC EFFECT IN HEPATOCELLULAR CARCINOMA DEVELOPMENT IN VIVO AND IN VITRO MODEL BY INHIBITING TGF-β1/pERK SIGNALING PATHWAY
Introduction and Objectives: Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins may reduce HCC incidence. Its antitumor activities are controversial and may be mediated by disrupting several hepatocarcinogenic pathways. This study aimed to evaluate in vivo and in vitro the anti-p...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Annals of Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268123000340 |
| _version_ | 1797862178775105536 |
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| author | Ezequiel Ridruejo Zahira Deza Giselle Romero Caimi Lucia Coli AndLaura Alvarez |
| author_facet | Ezequiel Ridruejo Zahira Deza Giselle Romero Caimi Lucia Coli AndLaura Alvarez |
| author_sort | Ezequiel Ridruejo |
| collection | DOAJ |
| description | Introduction and Objectives: Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins may reduce HCC incidence. Its antitumor activities are controversial and may be mediated by disrupting several hepatocarcinogenic pathways. This study aimed to evaluate in vivo and in vitro the anti-proliferative and anti-angiogenic action of atorvastatin (AT) in the development of HCC as well as its mechanisms of action. Materials and Methods: In vivo model: the pesticide hexachlorobenzene (HCB) was used to promote the development of HCC in Balb/C nude mice inoculated with Hep-G2 cells. Tumor hepatic number, cell proliferation parameters (proliferating cell nuclear antigen, PCNA), cholesterol metabolism (3-hydroxy-3-methylglutaryl-coenzyme-A-reductase, HMGCoAR), angiogenesis and VEGF levels were analyzed. In vitro model: Hep-G2 and Ea-hy926 cells were used to evaluate the effect of AT (2,5; 5 and 5 mg/kg b.w.) on HCB-induced cell proliferation, migration, and vasculogenesis and analyze proliferative parameters. Results: In vivo: AT 5 mg/kg prevented liver growth and tumor development and inhibited PCNA, TGF-β1 and pERK levels increase. AT 5 mg/kg prevented VEGF levels and skin blood vessel formation. In vitro, AT prevented cell proliferation and migration as well as tubular formation in the endothelial cell line by inhibiting the TGF-β1/p ERK pathway. Conclusions: We were able to demonstrate the potential AT anti-proliferative and anti-angiogenic effects in an HCC model and the involvement of TGF-β1 and pERK pathways. |
| first_indexed | 2024-04-09T22:16:07Z |
| format | Article |
| id | doaj.art-5fe51b5239084c07813c8441ccdcee22 |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-04-09T22:16:07Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-5fe51b5239084c07813c8441ccdcee222023-03-23T04:33:59ZengElsevierAnnals of Hepatology1665-26812023-03-0128100930P- 28 ATORVASTATIN SHOWS ANTI-PROMOTOR AND ANTI-NEOANGIOGENIC EFFECT IN HEPATOCELLULAR CARCINOMA DEVELOPMENT IN VIVO AND IN VITRO MODEL BY INHIBITING TGF-β1/pERK SIGNALING PATHWAYEzequiel Ridruejo0Zahira Deza1Giselle Romero Caimi2Lucia Coli3AndLaura Alvarez4Laboratory of Biological Effects of Environmental Contaminants. Department of Human Biochemistry, School of Medicine, University of Buenos Aires. Buenos Aires, Argentina; Chief, Hepatology Section, Department of Medicine. Center for Medical Education and Clinical Research “Norberto Quirno” (CEMIC). Buenos Aires, ArgentinaLaboratory of Biological Effects of Environmental Contaminants. Department of Human Biochemistry, School of Medicine, University of Buenos Aires. Buenos Aires, ArgentinaLaboratory of Biological Effects of Environmental Contaminants. Department of Human Biochemistry, School of Medicine, University of Buenos Aires. Buenos Aires, ArgentinaLaboratory of Biological Effects of Environmental Contaminants. Department of Human Biochemistry, School of Medicine, University of Buenos Aires. Buenos Aires, ArgentinaLaboratory of Biological Effects of Environmental Contaminants. Department of Human Biochemistry, School of Medicine, University of Buenos Aires. Buenos Aires, ArgentinaIntroduction and Objectives: Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins may reduce HCC incidence. Its antitumor activities are controversial and may be mediated by disrupting several hepatocarcinogenic pathways. This study aimed to evaluate in vivo and in vitro the anti-proliferative and anti-angiogenic action of atorvastatin (AT) in the development of HCC as well as its mechanisms of action. Materials and Methods: In vivo model: the pesticide hexachlorobenzene (HCB) was used to promote the development of HCC in Balb/C nude mice inoculated with Hep-G2 cells. Tumor hepatic number, cell proliferation parameters (proliferating cell nuclear antigen, PCNA), cholesterol metabolism (3-hydroxy-3-methylglutaryl-coenzyme-A-reductase, HMGCoAR), angiogenesis and VEGF levels were analyzed. In vitro model: Hep-G2 and Ea-hy926 cells were used to evaluate the effect of AT (2,5; 5 and 5 mg/kg b.w.) on HCB-induced cell proliferation, migration, and vasculogenesis and analyze proliferative parameters. Results: In vivo: AT 5 mg/kg prevented liver growth and tumor development and inhibited PCNA, TGF-β1 and pERK levels increase. AT 5 mg/kg prevented VEGF levels and skin blood vessel formation. In vitro, AT prevented cell proliferation and migration as well as tubular formation in the endothelial cell line by inhibiting the TGF-β1/p ERK pathway. Conclusions: We were able to demonstrate the potential AT anti-proliferative and anti-angiogenic effects in an HCC model and the involvement of TGF-β1 and pERK pathways.http://www.sciencedirect.com/science/article/pii/S1665268123000340 |
| spellingShingle | Ezequiel Ridruejo Zahira Deza Giselle Romero Caimi Lucia Coli AndLaura Alvarez P- 28 ATORVASTATIN SHOWS ANTI-PROMOTOR AND ANTI-NEOANGIOGENIC EFFECT IN HEPATOCELLULAR CARCINOMA DEVELOPMENT IN VIVO AND IN VITRO MODEL BY INHIBITING TGF-β1/pERK SIGNALING PATHWAY Annals of Hepatology |
| title | P- 28 ATORVASTATIN SHOWS ANTI-PROMOTOR AND ANTI-NEOANGIOGENIC EFFECT IN HEPATOCELLULAR CARCINOMA DEVELOPMENT IN VIVO AND IN VITRO MODEL BY INHIBITING TGF-β1/pERK SIGNALING PATHWAY |
| title_full | P- 28 ATORVASTATIN SHOWS ANTI-PROMOTOR AND ANTI-NEOANGIOGENIC EFFECT IN HEPATOCELLULAR CARCINOMA DEVELOPMENT IN VIVO AND IN VITRO MODEL BY INHIBITING TGF-β1/pERK SIGNALING PATHWAY |
| title_fullStr | P- 28 ATORVASTATIN SHOWS ANTI-PROMOTOR AND ANTI-NEOANGIOGENIC EFFECT IN HEPATOCELLULAR CARCINOMA DEVELOPMENT IN VIVO AND IN VITRO MODEL BY INHIBITING TGF-β1/pERK SIGNALING PATHWAY |
| title_full_unstemmed | P- 28 ATORVASTATIN SHOWS ANTI-PROMOTOR AND ANTI-NEOANGIOGENIC EFFECT IN HEPATOCELLULAR CARCINOMA DEVELOPMENT IN VIVO AND IN VITRO MODEL BY INHIBITING TGF-β1/pERK SIGNALING PATHWAY |
| title_short | P- 28 ATORVASTATIN SHOWS ANTI-PROMOTOR AND ANTI-NEOANGIOGENIC EFFECT IN HEPATOCELLULAR CARCINOMA DEVELOPMENT IN VIVO AND IN VITRO MODEL BY INHIBITING TGF-β1/pERK SIGNALING PATHWAY |
| title_sort | p 28 atorvastatin shows anti promotor and anti neoangiogenic effect in hepatocellular carcinoma development in vivo and in vitro model by inhibiting tgf β1 perk signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S1665268123000340 |
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