Hepatocellular Carcinoma remains a major fatal disease that is resistant to most cytotoxic therapeutics owed to
the aberrant activation of signalling cascades. Recent patents reveal a new family of drugs that has been studied for
molecularly targeting these cascades; multi-kinase inhibitors, are nowadays considered as novel therapeutic approaches.
Therefore in this study, we aimed at investigating the impact of Imatinib mesylate, a tyrosine kinase inhibitor, on Human
Hepatoma (HuH-7) cellular behavior and specifically its effect on p53 tumor suppressor gene. HuH-7 cells were transfected
with a reporter vector containing a specific enhancer element that is activated upon binding to intracellular p53;
consequently downstream luciferase reporter gene is activated. Cells were treated with Imatinib and we looked for p53 induction
upon drug stimulation. Additionally; viability, metabolism, proliferation and apoptosis were evaluated. Upon
Imatinib treatment, p53 expression showed a significant increase represented in increased luminescence. Moreover; a decrease
in cellular viability and metabolic activity along with a considerable inhibition of proliferation and a vast increase
in Caspase 9 activity were observed when compared to untreated cells. This study suggests that the effects of Imatinib
mesylate might be attributable to enhanced active p53 in HuH-7 cells with consequent reduction in cancer progression
properties. The article also summarizes some recent relevant patents.
Keywords: Hepatocellular carcinoma, HuH-7, imatinib mesylate, luciferase reporter gene, molecular targeted therapy, p53, MAPK, Gastrointestinal Tumors, Functional Integrity Assay
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