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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). |