الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 208 |  |  |
| | | from | 208 | | |
Abstract
Breast cancer is the most common cancer among women. Animal experimental models are particularly helpful in studying human carcinogenesis since the rat mammary gland is extremely prone to developing neoplasms, which closely mimic human breast cancer. 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer in female Sprague Dawley rats is regarded as a standard laboratory model of mammary carcinogenesis. It can induce molecular, biochemical, genetic, and histopathological changes in rats which mimic those observed in human cancers. Therefore, the evaluation of DMBA-induced carcinogenesis may help in treatment monitoring and screening for effective anti-cancer drugs. The main trending treatments for breast cancer are surgery, chemotherapy, radiation, hormonal, and targeted therapy. Anthracyclines (including doxorubicin (DOX)) are still the backbone of commonly used breast cancer chemotherapy regimens. However, single-agent chemotherapy is no longer suitable for treating cancer because of its induced side effects and development of cancer cell resistance. In context, combination therapy could offer a superior treatment outcome by augmenting the efficiency of chemotherapeutic drugs and overcoming both multidrug resistance and side effects. In this study, we first aimed to investigate the antitumor efficacy of the antiretroviral, tenofovir disoproxil fumarate disoproxil fumarate (TF), and the vitamin E analog, tiron (TR), either alone or combined with DOX against DMBA-induced breast cancer via controlling Notch signaling as a major driver for breast cancer development and as a key mechanism of multidrug resistance in cancer cells. The second point is to ensure the safety of such combination therapy by assessing its effect on the heart to reach doses that are not only effective but also safer. Our present study showed the potential use of TF (25 or 50 mg/kg) and TR (100 and 200 mg/kg) as antitumor agents in DMBA-induced breast cancer. To the best of our knowledge, this study provides for the first time new insights toward using DOX (2 mg/kg) + TF (50 mg/kg) and DOX (2 mg/kg) + TR (200 mg/kg) combinations which exert excellent antitumor activity with additional advantages of evading cancer cell resistance and superior cardiac safety profile. Cancer treatment has become more and more challenging. However, combination treatment is regarded to be a promising therapeutic strategy with higher efficacy and reduced side effects. It is recommended to conduct more investigations to elucidate the potential antitumor effects of these combinations in reduced doses as treatment protocols. Further clinical studies in breast cancer patients are required to evaluate the antitumor activity of DOX + TF and DOX + TR combinations that surpass DOX alone in avoiding the likelihood of chemoresistance and having a good cardiac safety index.