Transforming growth factor-β (TGF-β) superfamily plays a significant role in ovarian physiology but dysregulated TGF-β signaling is associated with promotion of ovarian carcinogenesis. TGF-β signaling in ovarian cancer favors cancer invasion and metastasis and controls ovarian cancer cell proliferation. The objective of this study is to determine the ability of a food-derived peptide, called BG-4, to suppress TGF-β1 signaling in ovarian cancer cells. BG-4 is a novel bioactive peptide isolated from the seeds of Momordica charantia with demonstrated anticancer and strong trypsin inhibitory properties. Different ovarian cancer cells (A2780-1A9, BR and PEO4) were exposed to 10 ng/mL TGF-β1 with or without non-cytotoxic dose of BG-4 (100 µg/mL) and response to chemotherapeutic reagents paclitaxel and cisplatin was evaluated. In addition, markers of epithelial-to-mesenchymal transition (EMT) and apoptosis were evaluated using western blot and immunofluorescence microscopy. TGF-β1 treatment resulted in cisplatin resistance in three cell lines as evidenced by increase in ED50 values from 42.9 µM to 88.5 µM, 53.7 µM to 108.3 µM and 44.8 µM to 67.3 µM for BR, PEO4 and A2780-1A9 cells, respectively. In the presence of BG-4, ED50 values of 35.6 µM, 56.4 µM and 46.6 µM were obtained for BR, PEO4 and A2780-1A9 cells, respectively. These values are similar to non-TGF-β1-treated cells indicating the ability of BG-4 to reverse TGF-β1-induced chemoresistance in ovarian cancer cell lines. Mechanistic studies showed that TGF-β1 signaling induces EMT in ovarian cancer cells as shown by differential expression of epithelial marker E-cadherin and mesenchymal markers N-cadherin, vimentin and transcription factors Snail, Slug and Twist1. In addition, the expression of apoptosis markers were affected by TGF-β1 signaling. On the other hand, treatment of TGF-β1 in the presence of 100 µg/mL BG-4 led to reversal of the EMT process. These results showed that the ability of BG-4 to reverse TGF-β1-induced chemoresistance in ovarian cancer cell lines may be associated with inhibition of the EMT process.
Citation Format: Vermont P Dia. TGF-β1-INDUCED CHEMORESISTANCE IS REVERSED BY BG-4 PEPTIDE [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-091.