Effect and significance of sunitinib on gefitinib resistance of lung cancer cells / 中国药学杂志

ABSTRACT

OBJECTIVE: To explore effection and significance of sunitinib on gefitinib resistance of lung cancer cells. METHODS: Cell proliferation inhibition of 28 gefitinib resistance lung cancer patients tumor tissues extracted with sunitinib treatment were measured using MTT assay. After sunitinib treatment, sensitivity of gefitinib resistance cells were measured by CellTiter-Glo method;The accumulation of Rh-123 in gefitinib resistant cells with sunitinib treatment were measured by FCM method. Accumulation of multi-drug resistance protein (MDR), transcription factors κB(NF-κB)and vascular endothelial growth factor(VEGF) were examined using Western blotting after sunitinib treatment on gefitinib resistance cells. RESULTS: Cell proliferation were inhibited by dose dependent after sunitinib treatment, IC50 is (6.73±1.57) μmol·L-1. Sensitivity of gefitinib resistance cells were significantly increased, and decreased the IC50 of gefitinib for inhibiting resistance cells after 1 and 2 μmol·L-1 sunitinib combine with gefitinib treatment, IC50 of gefitinib is (38.64±1.29) and (20.37±1.75) μmol·L-1 respectively. The accumulation of Rh-123 in gefitinib resistant cells with 1 μmol·L-1 sunitinib treatment were significantly increased(P<0.05), fluorescent density increased by 2.44 times following treatment with 1 μmol·L-1 of sunitinib, accumulation of Rh-123 in gefitinib resistant cells with 2 μmol·L-1 sunitinib treatment is larger significantly increased(P<0.01), fluorescent density increased by 5.64 times following treatment with 2 μmol·L-1 of sunitinib; expression level of MDR, NF-κB and VEGF proteins were significantly reduced after 1 and 2 μmol·L-1 sunitinib treatment. CONCLUSION: Sunitinib is able to reverse the gefitinib resistance, the theoretical foundation is provided for clinical treatment of patients with gefitinib resistance.