© 2019, Hacettepe University, Faculty of Pharmacy. All rights reserved.Despite the developments in the modern medicine, the resistancy to adjuvant/neoadjuvant therapies is one of the most important problem that may complicate the treatment. In recent years, studies have shown that activation of epithelial-mesenchymal transition (EMT) may plays an important role in cancer cells tendency to metastasis and resistance to chemotherapy. In this work, in vitro EMT model was generated with Caco-2 cell line to determine the mechanisms of response and resistancy. This cells are well-known for their ability to transform and are important tools for structural and functional studies due to their differentiation potential. Differentiation was monitored on days 0th, 15th and 30th and epithelial and mesenchymal markers (E-cadherin and Vimentin) were used for model validation with qRT-PCR. Glutathione S-Transferase-π (GST-π) levels were determined to elucidate the mechanisms of resistancy in both forms of EMT with ELISA. As expected, it was shown that GST-π levels increased significantly in mesenchymal form. Also, GST-π inhibitor hypericin was used to eliminate resistancy in mesenchymal form. Significant decrease in GST-π levels was determined with the different concentrations of hypericin treatment (2μM and 20μM). These results showed that, activation of mechanisms to eliminate resistancy in addition to adjuvant therapy may increase the effectiveness of treatment.