Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Medical Biochemistry

Background: Hepatocarcinogenesis is a complex and multi-step process resulting from a combination of epigenetic and genetic alterations. Transforming growth factor-beta (TGF-Ý) signaling pathway has been recognized as a key driver in cancer, where its activation affects cell proliferation, angiogenesis, invasion and metastasis. We evaluated the effect of mesenchymal stem cells (MSCs) and vitamin D on TGF-Ý signaling in hepatocellular carcinoma (HCC), in vivo, on hepatoma induced animal model in rats. Also we investigated the effect of MSCs and vitamin D, in vitro, on hepatoma cell line (HepG2 cells). Results: TGF-Ý level and the gene expression of TGF-Ý downstream target genes (Smad3 and snail), in addition to Smad2 protein level in rat liver tissues were downregulated in all treated groups with more suppressive effect in the group treated with both MSCs and vitamin D. Serum levels of AFP and ALT were significantly decreased in all treated groups. Also, all treated HepG2 cells showed a significant increase in Bax and significant decrease in Bcl-2 gene expression, in addition to significant decrease in HepG2 cell proliferation rate. Histopathological examination of liver tissue from induced HCC rats which received DENA-CCl4 only, revealed dysplastic cirrhotic nodules and solid areas of neoplasia. Administration of MSCs or vitamin D into induced HCC rats improved the histopathological picture with residual pathology, while administration of both MSCs and vitamin D showed restoration of liver parenchyma

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