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- W2222700962 abstract "Objective: To explore the efficacy of sunitinib as a single agent and in combination with docetaxel under three different sequence-dependent schedules on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) -resistant human non-small cell lung cancer A549 cells, and to reveal the responsible mechanisms for generating these differences. Methods: The half inhibitory concentration (IC50) and the combination index (CI) values of docetaxel or sunitinib alone as well as in combination under three different sequence-schedules for A549 cells were estimated by MTT. The flow cytometry (FCM) was used to analyze the alteration of cell cycle in A549 cells treated with sunitinib (3.5 μmol/L) and docetaxel (5.0 nmol/L) by different administration programs. The change of p-AKT protein level under different sequence-schedules was measured by Western blotting. Results: At 72 h, the IC50 values of docetaxel and sunitinib for A549 cells were 3.6±0.41 μmol/L and 5.5±0.95 nmol/L, respectively. The synergic effect of combination therapy with docetaxel and sunitinib was associated with the sequence of administration. The sequence of docetaxel followed by sunitinib showed a significant synergic effect; however, when the two drugs were used concurrently or by the reverse sequence, they illustrated an antagonistic effect. FCM analysis showed that sunitinib resulted in cell cycle arrest at G0/G1 phase, while docetaxel induced cell cycle arrest at S phase. When docetaxel was administered followed by sunitinib, the percentages of S-phase and G0/G1-phase cells were significantly increased and decreased, respectively. The ratio of p-AKT/AKT reached its lowest level in A549 cells treated with docetaxel followed by sunitinib. Conclusion: Sunitinib can inhibit the growth of A549 cells. The sequence of docetaxel followed by sunitinib can produce significant synergism. The mechanism underlying the difference may be related to the changes of cell cycle and the survival pathway.DOI: 10.3781/j.issn.1000-7431.2011.09.006" @default.
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- W2222700962 date "2011-09-25" @default.
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- W2222700962 title "Schedule-dependent cytotoxic synergism of docetaxel and sunitinib in EGFR-TKIs-resistant human non-small cell lung cancer cell line A549" @default.
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