Establishment of the Clone of Gastrointestinal Stromal Tumor Cells with the Signs of Multiple Drug Resistance and Assessment of Its Properties
The aim of the investigation was to obtain a tumor cell clone of gastrointestinal stromal tumors (GISTs) possessing resistance to chemotherapeutic agents of different mode of action, and to assess its sensitivity to various groups of chemotherapeutic agents.
Materials and Methods. GIST cell line T-1 was used to obtain a clone of chemoresistant GIST cells. The viability assessment of tumor cells was carried out by using i-CELLigence RTCA cell analyzer (ACEA Biosciences, USA). The sensitivity of GIST T-1-29R cell clone to type II topoisomerase inhibitors (doxorubicin and etoposide); chemotherapeutic agents affecting the dynamic state of the spindle microtubules (vinblastine and paclitaxel); hydroxyurea; cisplatin; targeted drug imatinib were evaluated by using the MTT-based assay. Expression of apoptosis, the markers of DNA damage and chemoresistance was examined by immunoblotting.
Results. A clone of GIST T-1 tumor cell line with the signs of chemoresistance (T-1-29R) was obtained after 8-month of cultivation of GIST tumor cells in the presence of the gradually increasing doses of paclitaxel. T-1-29R cells were found to possess resistance to paclitaxel, and cross-resistance to doxorubicin and etoposide, as well. Sensitivity of T-1-29R cells to other chemotherapeutic agents, including imatinib, did not change. Some multiple drug resistance proteins, e.g. MDR-1, were revealed to have an increased expression level in T-1-29R tumor cells when compared to parent T-1 cells.
Conclusion. A clone of GIST T-1-29R cell line possesses phenotypical features of multiple drug resistance, that makes its perspective use for the assessment of GIST chemosensitivity, and for screening of new compounds for their cytotoxic and antitumor activities in vitro and in vivo, as well.
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