Pan, F and Tian, J and Zhang, X and Zhang, Y and Pan, Y, Synergistic interaction between sunitinib and docetaxel is sequence dependent in human non-small lung cancer with EGFR TKIs-resistant mutation, Journal of Cancer Research and Clinical Oncology, 137, (9) pp. 1397-1408. ISSN 0171-5216 (2011) [Refereed Article]
Copyright Springer-Verlag 2011
Methods: NSCLC cell lines with EGFR T790M mutation and K-ras mutation were exposed to either sunitinib or docetaxel or both based on various sequential administrations. After exposure, the cell viability was measured by MTT assay, cell cycle distribution was analyzed by flow cytometry, and alterations in signaling pathway were determined by immunoblotting.
Results: Sunitinib exhibited dose-dependent growth inhibition in NSCLC cell lines and arrested cell cycle at G1 phase, whereas docetaxel arrested at S phase. Although single or concurrent use of sunitinib and docetaxel has some anti-proliferative effects, the sequential administrations of both drugs remarkably enhanced anti-tumor activity. When cells were exposed to docetaxel followed by sunitinib, synergism was observed. The molecular basis of this synergism is that the signaling pathways that were initially activated by docetaxel exposure were efficiently suppressed by the subsequent exposure to sunitinib. In contrast, the reverse of this sequential administration resulted in antagonism, which may be due to differential effects on cell cycle arrest.
Conclusions: Sunitinib as a single agent exhibits anti-proliferative effects in vitro in NSCLC cell lines with EGFR T790M and K-ras mutations but the sequential administration of docetaxel followed by sunitinib is superior to sunitinib followed by docetaxel and concurrent administration.
|Item Type:||Refereed Article|
|Keywords:||sunitinib, docetaxel, NSCLC, sequence treatment|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Oncology and carcinogenesis|
|Research Field:||Cancer cell biology|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Pan, F (Dr Feng Pan)|
|Web of Science® Times Cited:||17|
|Deposited By:||Menzies Institute for Medical Research|
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