Inhibition effect of Peg-IFNα-2b and Imatinib alone or combination on imatinib-resistant gastrointestinal stromal...

To investigate the inhibition effect of polyethylene glycol interferon α-2b and imatinib alone or combination on imatinib-resistant GIST cell lines, and to explore the possible mechanism. Imatinib resistant GIST cell lines (GIST-R) were exposured to either Peg-IFNα-2b or imatinib alone or combination. The proliferative inhibition rates and the combination index (CI) values of GIST-R cells were detected by MTT assay. The apoptotic rates of GIST-R cells were detected by flow cytometry. The expression levels of phospho-mammalian target of rapamycin (p-mTOR), and Bcl-2 of GIST-R cells were analyzed by Western blot. GIST-R cells presents remarkable resistance to imatinib, and the resistance index (RI) were (P<0.05). And The proliferative inhibition rate and the apoptotic rate of GIST-R cells in combination of Peg-IFNα2b and Imatinib group were higher than those in Peg-IFNα-2b or imatinib alone group (P<0.05). The CI value of Peg-IFNα-2b and imatinib was less than each alone, which had a synergistic effect (CI=0.63). As compared with the control (GIST-R cells without any treatment), the expression levels of p-mTOR and Bcl-2 proteins of GIST-R cells in combination of Peg-IFNα-2b and imatinib group were decreased (P<0.01). The combination of Peg-IFNα-2b and imatinib generats a synergistic effect in GIST-R cells, and reversal of drug resistance. This effect may be related with apoptosis and down-regulation of the expression of p-mTOR.