Open Access

Cancer‑associated fibroblast‑derived CCL5 contributes to cisplatin resistance in A549 NSCLC cells partially through upregulation of lncRNA HOTAIR expression

  • Authors:
    • Xiangjun Sun
    • Zhijie Chen
  • View Affiliations

  • Published online on: August 2, 2021     https://doi.org/10.3892/ol.2021.12957
  • Article Number: 696
  • Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Aberrant C‑C motif chemokine ligand 5 (CCL5) is associated with disease progression, poor prognosis and chemotherapy resistance in human malignancy. The tumor microenvironment (TME) contributes to chemotherapy resistance. However, the role of cancer‑associated fibroblasts (CAFs)‑derived CCL5 is not well documented. Hence, the present study aimed to investigate the effects of CAFs on chemotherapy resistance in A549 non‑small cell lung cancer (NSCLC) cells and the underlying mechanism. Primary CAFs isolated from patients with NSCLC were found to express and secrete elevated levels of CCL5, which attenuated cisplatin (DDP)‑induced apoptosis, as indicated by flow cytometry analysis. In addition, CCL5 upregulated the expression levels of long non‑coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in the tumor cells, and silencing HOTAIR in tumor cells enhanced the cytotoxic effect of cisplatin, characterized by decreased cell viability and increased apoptotic rate. Mechanistically, HOTAIR was found to inactivate the caspase‑3/BCL‑2 signaling pathway in A549 NSCLC cells. Collectively, the current study demonstrated that CAFs in the TME may serve a crucial role in the higher expression levels of CCL5 in tumors and that CAF‑derived CCL5 may promote cisplatin resistance via upregulating lncRNA HOTAIR expression.
View Figures
View References

Related Articles

Journal Cover

October-2021
Volume 22 Issue 4

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Sun X and Sun X: Cancer‑associated fibroblast‑derived CCL5 contributes to cisplatin resistance in A549 NSCLC cells partially through upregulation of lncRNA HOTAIR expression. Oncol Lett 22: 696, 2021
APA
Sun, X., & Sun, X. (2021). Cancer‑associated fibroblast‑derived CCL5 contributes to cisplatin resistance in A549 NSCLC cells partially through upregulation of lncRNA HOTAIR expression. Oncology Letters, 22, 696. https://doi.org/10.3892/ol.2021.12957
MLA
Sun, X., Chen, Z."Cancer‑associated fibroblast‑derived CCL5 contributes to cisplatin resistance in A549 NSCLC cells partially through upregulation of lncRNA HOTAIR expression". Oncology Letters 22.4 (2021): 696.
Chicago
Sun, X., Chen, Z."Cancer‑associated fibroblast‑derived CCL5 contributes to cisplatin resistance in A549 NSCLC cells partially through upregulation of lncRNA HOTAIR expression". Oncology Letters 22, no. 4 (2021): 696. https://doi.org/10.3892/ol.2021.12957