الفهرس 
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Abstract
introductlon : Head and neck cancer (HNC) is one of the most common causes of
death in human. In most cases, its treatment involves chemotherapy(1).
However, the drug toxicity and/or tumor cell resistance are obstacles to
the choice of chemotherapy(2). Scientific studies proved that combining
chemotherapy with specific antioxidants, at defined dosages can
improve drug efficacy and/or may reduce the severity of side effects(3,4).
DOI: 10.21608/dsu.2020.30956.1038
Manuscript ID: DSU-2005-1038
KEYWORDS
Chemotherapy;
Fluorouracil; IHC;
Oral Squamous Cell
Carcinoma;
p53; Rat tongue; Resveratrol.
• E-mail address:
dinaelorabyy@gmail.com
1. Postgraduate student of Oral
Pathology, Faculty of Dentistry, Suez Canal University,
Ismailia, Egypt
2. Professor of Oral Pathology,
Faculty of Dentistry, Suez
Canal University, Ismailia,
Egypt
3. Professor of Oral Pathology,
Faculty of Dentistry, Misr
International University,
Cairo,Egypt
4. Associate Professor of Oral
Pathology, Faculty of Dentistry, Suez Canal University,
Ismailia, Egypt
SYNERGISTIC EFFECT OF RESVERATROL WITH 5-FLUOROURACIL IN
CHEMOTHERAPY OF INDUCED ORAL SQUAMOUS CELL CARCINOMA
Dina Ashraf Ibrahim El-Oraby1
, Magda Mohamed Aly Hassan2
, Marwa Mokbel El-Shafei3
,
Wafaa Hassanein El-Hossary4
162
Dina Ashraf Ibrahim El-Oraby, et al.
The most commonly used chemotherapeutic
drug is 5-fluorouracil (5-FU) in treatment of oral,
breast, stomach and pancreatic cancer, that remains
the cornerstone of chemotherapy(5,6). It has been
widely used in combination with other drugs as
well. Many of these effective drugs have been developed from botanical sources(7).
Due to the side effects of 5-FU in chemotherapy, an introduction of a natural extract had been
used in different in vivo studies to enhance the
efficacy of chemotherapy, reduce the treatment
duration, reduce the expected dose and in turn its
toxicity.7 Resveratrol (RV) is one of the natural extracts that plays a synergistic effect with 5-FU, as
revealed in a recent study on rat colorectal cancer(4).
It’s effects include antibacterial, antifungal, antioxidant (through scavenging reactive oxygen species
(ROS)(8), stimulates cell cycle arrest, that in turn
stimulates apoptosis(9). It inhibits invasion and metastasis through modulation of ecto-mesenchymal
transition(10). Furthermore, it leads to protein kinases
inhibition, antiapoptotic gene expression, as well as
angiogenic, metastatic gene products and inflammatory biomarkers(11).
P53 is an intensively studied tumor suppressor
gene. When mutated , it leads to loss of wild type p53
activity.12 Disturbances in P53 signaling pathways
are believed to be required for the development
of most cancers, and there is evidence to suggest
that its restoration or reactivation will lead to a
therapeutic benefit(12–14).
For studying oral cancer prevention and
treatment, one of the most commonly used animal
model is cancer induction in the rat tongue, by the
water-soluble 4-nitroquinoline1-oxide (4NQO)(15).
Chronic administration of 4NQO induces rat tongue
cancer at the same manner that occurs in humans, in
terms of initiation, promotion, and progression(16).