期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 21, 页码 -出版社
MDPI
DOI: 10.3390/ijms222111360
关键词
HCC; PPAR gamma; inflammation; apoptosis; liver cancer
资金
- CONACyT for Basic Science [259096 CB-2015-01]
- PRODEP-SEP
- Apoyo a la Incorporacion de Nuevos Profesores de Tiempo Completo [PTC-1565]
- CONACyT [461588]
The study evaluated the effects of PFD on early stages of liver cancer development, showing that PFD can prevent tissue damage, reduce fibrosis and inflammation, and promote apoptosis in the experimental model.
Targeted therapies for regulating processes such as inflammation, apoptosis, and fibrogenesis might modulate human HCC development. Pirfenidone (PFD) has shown anti-fibrotic and anti-inflammatory functions in both clinical and experimental studies. The aim of this study was to evaluate PPAR gamma expression and localization in samples of primary human tumors and assess PFD-effect in early phases of hepatocarcinogenic process. Human HCC tissue samples were obtained by surgical resection. Experimental hepatocarcinogenesis was induced in male Fischer-344 rats. TGF-beta 1 and alpha-SMA expression was evaluated as fibrosis markers. NF-kB cascade, TNF alpha, IL-6, and COX-2 expression and localization were evaluated as inflammation indicators. Caspase-3, p53, and PARP-1 were used as apoptosis markers, PCNA for proliferation. Finally, PPAR alpha and PPAR gamma expression were evaluated to understand the effect of PFD on the activation of such pathways. PPAR gamma expression was predominantly localized in cytoplasm in human HCC tissue. PFD was effective to prevent histopathological damage and TGF-beta 1 and alpha-SMA overexpression in the experimental model. Anti-inflammatory effects of PFD correlate with diminished IKK and decrease in both IkB-phosphorylation/NF-kB p65 expression and p65-translocation into the nucleus. Pro-apoptotic PFD-induced effects are related with p53 expression, Caspase-3 p17 activation, and PARP-1-cleavage. In conclusion, PFD acts as a tumor suppressor by preventing fibrosis, reducing inflammation, and promoting apoptosis in MRHM.
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