alexa Expression Of Antimicrobial Peptide Hcap18/LL-37 Following Non-viral Delivery Of Plasmid DNA Encoded By CAMP Gene In Human Fibroblasts And Keratinocytes
ISSN: 2167-7689

Pharmaceutical Regulatory Affairs: Open Access
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9th Annual European Pharma Congress
June 26-28, 2017 Madrid, Spain

Nahla E El-Ashmawy, Naglaa F Khedr, Hoda A El-Bahrawy and Hend E Abo Mansour
Tanta University, Egypt
Posters & Accepted Abstracts: Pharmaceut Reg Affairs
DOI: 10.4172/2167-7689-C1-025
Abstract
Since the incidence of breast cancer increases dramatically all over the world, the search for effective treatment is an urgent need. Metformin (MET) has demonstrated anti-tumorigenic effect both in vivo and in vitro in different cancer types. The present work was designed to examine on molecular level the mode of action of MET in mice bearing Solid Ehrlich Carcinoma (SEC) and to evaluate the use of MET in conjunction with doxorubicin (DOX) as a combined therapy against SEC. Ehrlich ascites carcinoma cells were inoculated in 60 female mice as a model of breast cancer. The mice were divided into four equal groups: Control tumor, MET, DOX and co-treatment. MET (15 mg/kg) and DOX (4 mg/kg) were given i.p. for four cycles every five days starting on day 12 of inoculation. The anti-tumorigenic effect of MET was mediated by enhancement of adenosine monophosphate protein kinase (AMPK) activity and elevation of P53 protein as well as the suppression of nuclear factor-kappa B (NF-5B), DNA contents and cyclin D1 gene expression. MET and DOX mono-treatments exhibited opposing action regarding cyclin D1 gene expression, phosphorylated- AMPK (PAMPK) and NF-5B levels. Co-treatment markedly decreased tumor volume, increased survival rate and improved other parameters compared to DOX group. In parallel, the histopathological findings demonstrated enhanced apoptosis and absence of necrosis in tumor tissue of co-treatment group. MET proved chemotherapeutic effect which could be mediated by the activation of AMPK and related pathways. Combining MET and DOX, which exhibited different mechanisms of action, produced greater efficacy as anticancer therapeutic regimen.
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