Abstract

TGF alpha L3-SEB is a new synthetic fusion protein produced by the combination of the third loop of transforming growth factor with staphylococcal enterotoxin type B. In the current study, the anti-tumor effects of TGF alpha L3-SEB were evaluated against SKOV3 cells, which highly expressed the epidermal growth factor receptor (EGFR). Our findings showed that incubation of SKOV3 cells with 75, 100 and 150 mu g/ml of TGF alpha L3-SEB significantly reduces the proliferation rate in a concentration-dependent manner (P < 0.05) and its IC50 value was 110 mu g/ml. Caspase-3 activity was increased from 100 for control cells to 109, 144, and 169 for 75, 100 and 150 mu g/ml of TGF alpha L3-SEB treatment, respectively. Caspase-9 activity and bax/bcl-2 ratio were also confirmed the apoptosis induction ability of TGF alpha L3-SEB (P < 0.001). Flow cytometry examination also showed that apoptosis was induced and the number of apoptotic cells was increased from 8.2 in un-treated cells to 20.9, 50, and 90 in response to 75, 100 and 150 mu g/ml of TGF alpha L3-SEB fusion protein in a concentration-dependent manner (P < 0.05). The mRNA expression level of VEGF was also reduced to 0.89, 0.69, and 0.60, respectively in response to 75, 100 and 150 mu g/ml of TGF alpha L3-SEB fusion protein exposure, respectively (P < 0.5). In summary, the findings of our study uncovered that TGF alpha L3-SEB fusion protein induced apoptosis and reduced angiogenesis in SKOV3 ovarian cancer cells in a concentration-dependent manner. This protein has the potential to act against EGFR expressing malignant cells to serve as a pro-apoptotic and angiogenesis blocker agents; however, further studies are needed to confirm its ability.