الفهرس 
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Abstract
Most of oral cancers are squamous cell carcinomas representing a major
health problem which demands its prevention and treatment.
Therefore thorough understanding of the molecular mechanisms involved in
the initiation and progression of malignancy is essential to halt the tumor
progression.
Trials of various chemotherapeutic agents that target molecular genes have
been carried out aiming to help improving prognosis in cancer patients and
elaborating new forms of treatment.
Metformin, is one of the few FDA-approved anti-diabetic drugs owing to its
near-perfect safety record, low cost, and favorable side-effect profile,
metformin has been recently suggested as a chemo-therapeutic agent owing
to its inhibitory and apoptotic effects on cancer cells in many types of
cancers, however its action in oral cancers has not been well defined.
In the present study we showed the effect of metformin drug in various
concentrations 5, 10, and 20mmol for a period of 24, 48, and 72 hours on the
viability of cancer cells via MTT assay and also studied its effect on
mitochondrial COX-1 and cyclin D1 genes expression in HEp-2 squamous
cell carcinoma cell line using real time PCR.
Mitochondrial COX-1 is a key factor in aerobic metabolism and is the
subunit 1 of complex IV which represents the terminal, energy-transfer
enzyme of the respiratory chain, cyclin D1 is a positive regulator of the cell
cycle where it binds to complexes that promotes cell cycle progression and
thereby cell division, studies have shown that both these two genes arehighly expressed in cancer cells. The results of the present work showed that metformin significantly
decreased both the proliferation of cells and the expression of both genes in a
dose dependent manner with a significant positive direct linear correlation
between them over the whole period.
It was concluded from this study that metformin affects the viability of cells
through cell cycle arrest and apoptosis, Metformin could be recommended as
an effective anticancer agent preferably used at 48 hours with 10mmol
concentration