Gastrointestinal stromal tumor cell lines - the mechanisms of chemosensitivity in vitro

This research was aimed to study the sensitivity of gastrointestinal stromal tumors (GISTs) to chemotherapeutic drugs. We studied the chemosensitivity of GISTs by using several GIST cell lines. Cytotoxicity of chemotherapeutic drugs was assessed by colorometric MTS-assay. The expression level of DNA damage markers and repair proteins was assessed by immunoblotting. Apoptosis analysis was conducted by measuring the amount of hypodiploid cells by using a propidium iodide DNA staining procedure and flow cytometry analysis. We found that GISTs are sensitive to certain chemotherapeutic drugs - topoisomerase II inhibitors (etoposide and doxorubicine). DNA damage induction (in particular, DNA double-strand breaks formation) in GISTs induced cell apoptotic cell death despite the activation of DNA repair pathways. Of note, this effect was observed in imatinib-sensitive and resistant GIST cell lines, as well. We also found an increase accumulation phosphorylated form of histone 2A in GISTs after imatinib treatment. This effect was associated with the significant reduction of Rad51 recombinase expression, known as a key factor of homologous recombination. Taken together, this might explain the possible mechanisms of cell death in GISTs after targeted therapy. We found the chemosensitivity of GIST cell lines to some certain chemotherapeutic agents. Thus, the current point of view indicating about GISTs resistance to chemotherapy is needed to be re-evaluated.

gastrointestinal tumors (GISTs), chemotherapeutic agents, imatinib, DNA damage and repair, apoptosis