Exosome‑mediated gefitinib resistance in lung cancer HCC827 cells via delivery of miR‑21

  • Authors:
    • Changwen Jing
    • Haixia Cao
    • Xiaobing Qin
    • Shaorong Yu
    • Jianzhong Wu
    • Zhuo Wang
    • Rong Ma
    • Jifeng Feng
  • View Affiliations

  • Published online on: April 27, 2018     https://doi.org/10.3892/ol.2018.8604
  • Pages: 9811-9817
  • Copyright: © Jing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acquired resistance to gefitinib remains a major challenge in cancer treatment. In the present study, the effect of exosomes on the transmission of gefitinib resistance from gefitinib‑resistant HCC827 lung cancer cells (H827R) to their gefitinib‑sensitive counterparts and the potential underlying mechanisms by which this occurs was investigated. Exosomes were obtained from the cell supernatant using ultracentrifugation and the ExoQuick‑TC exosome precipitation solution. Drug resistance was assessed by flow cytometry, apoptosis assays and cell counting kit‑8 assays. The expression of microRNA (miR)‑21 was analyzed by reverse transcription‑quantitative polymerase chain reaction. Exosomes released by H827R cells (R/exo) may decrease the sensitivity of the human NSCLC HCC827 cell line to gefitinib. The results indicated that miR‑21 expression was increased in R/exo and R/exo‑treated H827S cells. However, miR‑21 inhibition abrogated exosome‑mediated drug resistance. Phosphorylated‑protein kinase B (p‑Akt), which is downstream of miR‑21, was downregulated following gefitinib treatment; however, R/exo pretreatment elevated p‑Akt levels and promoted the activation of Akt. By contrast, miR‑21 inhibition reduced p‑Akt expression. Therefore, the induction of miR‑21 via exosomes and the activation of Akt may be mechanisms by which exosomes mediate the transfer of drug resistance.
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June-2018
Volume 15 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Jing C, Cao H, Qin X, Yu S, Wu J, Wang Z, Ma R and Feng J: Exosome‑mediated gefitinib resistance in lung cancer HCC827 cells via delivery of miR‑21. Oncol Lett 15: 9811-9817, 2018
APA
Jing, C., Cao, H., Qin, X., Yu, S., Wu, J., Wang, Z. ... Feng, J. (2018). Exosome‑mediated gefitinib resistance in lung cancer HCC827 cells via delivery of miR‑21. Oncology Letters, 15, 9811-9817. https://doi.org/10.3892/ol.2018.8604
MLA
Jing, C., Cao, H., Qin, X., Yu, S., Wu, J., Wang, Z., Ma, R., Feng, J."Exosome‑mediated gefitinib resistance in lung cancer HCC827 cells via delivery of miR‑21". Oncology Letters 15.6 (2018): 9811-9817.
Chicago
Jing, C., Cao, H., Qin, X., Yu, S., Wu, J., Wang, Z., Ma, R., Feng, J."Exosome‑mediated gefitinib resistance in lung cancer HCC827 cells via delivery of miR‑21". Oncology Letters 15, no. 6 (2018): 9811-9817. https://doi.org/10.3892/ol.2018.8604