Redistribution of DR4 and DR5 in lipid rafts accounts for the sensitivity to TRAIL in NSCLC cells

  • Authors:
    • Wen Ouyang
    • Chunxu Yang
    • Yu Liu
    • Jie Xiong
    • Junhong Zhang
    • Yahua Zhong
    • Gong Zhang
    • Fuxiang Zhou
    • Yunfeng Zhou
    • Conghua Xie
  • View Affiliations

  • Published online on: July 18, 2011     https://doi.org/10.3892/ijo.2011.1129
  • Pages: 1577-1586
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Abstract

The selective toxicity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) against tumor cells makes it a potential targeted drug for treating non-small cell lung carcinomas (NSCLC). However, the majority of established human NSCLC cell lines are either partially or completely resistant to TRAIL, resulting in the limitation for clinical use of rhTRAIL and its agonistic antibodies. In this study, compared to TRAIL-sensitive H460 cell line, TRAIL-resistant A549 cell line showed a similar expression level of DR5 and a higer expression level of DR4. It indicates that there is no positive correlation between the expression levels of death receptors and sensitivity to TRAIL. However, tests on A549 cells with DR4 siRNA transfection revealed that DR4-competitive binding to TRAIL could not affect the capacity of TRAIL in inducing apoptosis. Instead, further studies found that the aggregation of DR4 and DR5 in lipid rafts only occured in H460 cells with TRAIL pretreatment. It suggested that the TRAIL-induced redistribution of DR4 and DR5 in lipid rafts contributed to the sensitivity to TRAIL in TRAIL-sensitive NSCLC H460 cell line, which was also confirmed by intervention tests of the cholesterol-sequestering agent nystatin.

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December 2011
Volume 39 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ouyang W, Yang C, Liu Y, Xiong J, Zhang J, Zhong Y, Zhang G, Zhou F, Zhou Y, Xie C, Xie C, et al: Redistribution of DR4 and DR5 in lipid rafts accounts for the sensitivity to TRAIL in NSCLC cells. Int J Oncol 39: 1577-1586, 2011.
APA
Ouyang, W., Yang, C., Liu, Y., Xiong, J., Zhang, J., Zhong, Y. ... Xie, C. (2011). Redistribution of DR4 and DR5 in lipid rafts accounts for the sensitivity to TRAIL in NSCLC cells. International Journal of Oncology, 39, 1577-1586. https://doi.org/10.3892/ijo.2011.1129
MLA
Ouyang, W., Yang, C., Liu, Y., Xiong, J., Zhang, J., Zhong, Y., Zhang, G., Zhou, F., Zhou, Y., Xie, C."Redistribution of DR4 and DR5 in lipid rafts accounts for the sensitivity to TRAIL in NSCLC cells". International Journal of Oncology 39.6 (2011): 1577-1586.
Chicago
Ouyang, W., Yang, C., Liu, Y., Xiong, J., Zhang, J., Zhong, Y., Zhang, G., Zhou, F., Zhou, Y., Xie, C."Redistribution of DR4 and DR5 in lipid rafts accounts for the sensitivity to TRAIL in NSCLC cells". International Journal of Oncology 39, no. 6 (2011): 1577-1586. https://doi.org/10.3892/ijo.2011.1129