الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 232 |  |  |
| | | from | 232 | | |
Abstract
Triple-negative breast cancer (TNBC), as a subtype of breast cancer, can be defined as tumor that is negative for estrogen, progesterone and human epidermal growth factor receptors. Generally, the only current systemic treatment for TNBC is chemotherapy, anthracycline/taxane-based therapy. Due to the aggressive manner of the tumor, poor prognosis and present lack of targeted therapies. Alternative targeted therapies are essentially needed to improve clinical outcomes in TNBC patients. Despite being the primary treatment used for TNBC, DOX has only partial efficacy, and its cardiotoxicity is a limiting factor. Recently, the pro-apoptotic and anti-proliferative effects of copper (I) nicotinate (CNC) have been suggested in TNBC. Also, Torin1 (TOR), an ATP-competitive inhibitor of mTOR. the most commonly activated signaling pathway in human cancer. This pathway thus presents both an opportunity and a challenge for cancer therapy.
The present Study was designed to explore possible anti-carcinogenic effect of copper complex and Torin1 through angiogenesis in the triple negative breast cancer. Either alone or in the following combinations designed as the combination of DOX with either CNC or Torin1 and the combination of CNC with Torin1. All preformed combinations were an attempt for a novel strategy for TNBC treatment.
On the light of results of the present study it could be suggested that supplementation of TNBC patients with CNC/DOX, TOR/DOX or with CNC/TOR combinations would may have its impact on clinical outcome and low opportunities of developing adverse effects of these therapeutic agents. All of these may provide new insights into the development of tumor selective copper based anticancer therapeutic agents.
beside the ability of copper complex to induce cell death. the present study may reveal its anti-angiogenic effects, especially at low concentrations, as another important criterion.
The results also revealed that, TOR (mTOR inhibitor) significantly arrests the growth of TNBC cells. In addition, it significantly reduced angiogenesis through targeting multiple angiogenic factors as evidenced by the significant reduction of proangiogenic vascular endothelial growth factor, cluster of differentiation 34, and significant increase of anti-angiogenic endostatin. so TOR proved that it is powerful inhibitor with anti-angiogenic properties, suppressing cancer cell growth.