الفهرس 
General Overview
Role of cluster of differentiation 44Only 14 pages are availabe for public view
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Abstract
Breast cancer is the most common malignancy in females in almost all countries. World Health Organization (WHO) report shows that its incidence increases 2% per year. In Egypt, BC has been estimated to be the first cancer in women and the first leading cause of death among cancer patients. Its incidence has been gradually increasing in Egypt due to many etiological factors such as obesity, pollution, less physical exercise and environmental pollutants. Environmental factors that have been linked to BC are numerous one of which is food born carcinogens. PhIP is one of the most abundant heterocyclic amines (HCAs) in browned meat and fish. The HCAs found in food are formed when creatine, other amino acids, and monosaccharides, are heated together at high temperatures or cooked for relatively long periods of time. Long-terms studies of rats showed that PhIP causes several types of cancers including mammary carcinoma. Doxorubicin is one of the most important drugs for treatment of mammary carcinoma. Nevertheless, its use is limited due to the rapid development of chemoresistance and to the cardiotoxicity, so, combination with other drugs could be more useful. Preclinical studies have shown that metformin (the first line drug for treatment of type 2 diabetes) can inhibit the growth of cancer cells, including breast cancer in vitro and in vivo. The objective of this study is to explore the biochemical and molecular mechanisms that control the effects of metformin on the PhIP-induced mammary carcinomas in SD rats. Also, to investigate the potential utility of metformin in terms of potentiating the antitumor action of doxorubicin on PhIP-induced mammary carcinomas. One hundred and five female SD rats were divided randomly and equally into 7 groups (15 rats per group) as follows: Control group: Rats were administered 5% DMSO on days 1-5 and 8-12, then normal feeding without treatment for the rest of 26 weeks. Metformin group: Rats were administered metformin 2 mg/ml in the drinking water (Jeyabalan et al., 2013) starting from day 13 of the experiment to the end of the 26 weeks. Metformin+ Doxorubicin group: Rats were co-administered Metformin (2 mg/ml) in the drinking water starting from day 13 of the experiment and Doxorubicin (4 mg/kg b.wt./week, i.v.) (Wang et al., 2012) for 4 weeks, starting from day 43 of the experiment to the end of the 26 weeks. PhIP group: Rats were administered PhIP (75 mg/kg b.wt., p.o.) on days 1- 5 and 8-12 (Ghoshal et al., 1994). PhIP+Doxorubicin group: Rats were co-administered PhIP (75 mg/kg b.wt., p.o.) on days 1-5 and 8-12 and Doxorubicin (4 mg/kg b.wt./week, i.v.) for 4 weeks starting after one month of the last PhIP dose. PhIP+Metformin group: Rats were co-administered PhIP (75 mg/kg b.wt., p.o.) on days 1-5 and 8-12 and Metformin (2 mg/ml) in the drinking water starting after last PhIP dose (day 13) to the end of the 26 weeks. PhIP+Doxorubicin+Metformin group: Rats were co-administered PhIP (75 mg/kg b.wt., p.o.) on days 1-5 and 8-12 and Doxorubicin (4 mg/kg b.wt./week, i.v.) for 4 weeks starting after one month of the last PhIP dose in addition to Metformin (2 mg/ml) in the drinking water starting after last PhIP dose to the end of the 26 weeks.