Anti-angiogenic targeted therapy in triple negative breast cancer HCC-1806 cell line
Triple negative breast cancer (TNBC) is an aggressive tumor with poor prognosis, however, chemotherapy is the most important treatment for TNBC. It has been demonstrated that TNBC is markedly sensitive to anti-angiogenic therapy. In this context, PI3K/AKT/mTOR pathway may have a regulatory role in angiogenic output. Meanwhile, TORIN 1, PI3K/mTOR inhibitor, has been found to inhibit cell proliferation and it has been suggested that it may enhance the sensitivity of human TNBC cell line to doxorubicin. The present study was taken to explore the possible anti-angiogenic effects of TORIN 1, alone or in combination with therapeutic agent, doxorubicin (DOX) in HCC-1806 TNBC cell line. Cells were treated with two different concentrations of TORIN 1 (10% of IC50 and IC50). Also, cells were treated with concentrations equivalent to IC50 value of DOX. After each treatment, viability of cells was assessed by MTT assay in addition to quantification of VEGF gene expression and ES level, using RT-PCR and ELISA techniques, respectively. Treated cells were examined morphologically and the cell cycle was analyzed by flow cytometry. Moreover, evaluating CD34 protein expression using Western blotting technique was carried out. The results of the present study may lead to the suggestion that treating of TNBC patients with combination of TOR/DOX would have its impact on clinical outcome and low opportunities of developing adverse effects of chemotherapy. Index Terms— Angiogenesis, cluster of differentiation 34, Doxorubicin, Endostatin, Torin 1, Triple negative breast cancer