Cancer‑associated fibroblast‑derived CCL5 contributes to cisplatin resistance in A549 NSCLC cells partially through upregulation of lncRNA HOTAIR expression
Affiliations: Department of Respiratory and Critical Care Medicine, Hanchuan People's Hospital, Hanchuan, Hubei 431600, P.R. China, Department of General Surgery, Hanchuan People's Hospital, Hanchuan, Hubei 431600, P.R. China
- Published online on: August 2, 2021 https://doi.org/10.3892/ol.2021.12957
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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.