Effect and mechanism of Src tyrosine kinase inhibitor sunitinib on the drug-resistance reversal of human A549/DDP cisplatin-resistant lung cancer cell line

  • Authors:
    • Ke Zhang
    • Xian Wang
    • Hongyan Wang
  • View Affiliations

  • Published online on: August 4, 2014     https://doi.org/10.3892/mmr.2014.2440
  • Pages: 2065-2072
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Abstract

The development of tumor cell drug resistance is the primary reason for treatment failure in lung cancer chemotherapy. Therefore, overcoming multidrug resistance is currently an urgent issue to be addressed in lung cancer treatment. Sunitinib is a tyrosine kinase inhibitor with confirmed inhibitory effects on tumor growth and metastasis; however, the effects of sunitinib and mechanisms of action in lung cancer multidrug resistance are yet to be determined. The present study was designed to examine the effects of sunitinib and the mechanisms underlying lung cancer multidrug resistance. It was observed that sunitinib was able to improve the sensitivity of A549/DDP lung cancer cells to cisplatin, enhance tumor apoptosis, arrest the cell cycle in G0/G1 phase, upregulate intracellular Rh-123 content, downregulate the expression of P-glycoprotein, multidrug resistance protein 1, multidrug resistance-associated protein 1, lung resistance protein, glutathione-S-transferase, ERCC1, survivin and Bcl-2 in tumor cells, phosphorylation of AKT and extracellular signal‑regulated kinase (ERK), glutathione activity, and transcriptional activity of nuclear factor-κB, Twist, Snail and AP-1. The results demonstrated that sunitinib was able to reverse the multidrug resistance of A549/DDP lung cancer cells, which was possibly associated with the downregulation of multidrug resistance-associated gene expression and the inhibition of AKT and ERK phosphorylation.
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October 2014
Volume 10 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhang K, Wang X and Wang H: Effect and mechanism of Src tyrosine kinase inhibitor sunitinib on the drug-resistance reversal of human A549/DDP cisplatin-resistant lung cancer cell line. Mol Med Rep 10: 2065-2072, 2014
APA
Zhang, K., Wang, X., & Wang, H. (2014). Effect and mechanism of Src tyrosine kinase inhibitor sunitinib on the drug-resistance reversal of human A549/DDP cisplatin-resistant lung cancer cell line. Molecular Medicine Reports, 10, 2065-2072. https://doi.org/10.3892/mmr.2014.2440
MLA
Zhang, K., Wang, X., Wang, H."Effect and mechanism of Src tyrosine kinase inhibitor sunitinib on the drug-resistance reversal of human A549/DDP cisplatin-resistant lung cancer cell line". Molecular Medicine Reports 10.4 (2014): 2065-2072.
Chicago
Zhang, K., Wang, X., Wang, H."Effect and mechanism of Src tyrosine kinase inhibitor sunitinib on the drug-resistance reversal of human A549/DDP cisplatin-resistant lung cancer cell line". Molecular Medicine Reports 10, no. 4 (2014): 2065-2072. https://doi.org/10.3892/mmr.2014.2440