Abstract |
Cisplatin-based chemotherapy is the first-line treatment for non-small cell lung cancer (NSCLC), but drug resistance occurs in most patients, leading to treatment failure. Recent studies have shown that epithelial-mesenchymal transition (EMT) is associated with drug resistance. However, the underlying mechanism is not entirely clear. In this study, first we showed significant positive correlation between the expression of ERCCl and vimentin, and significant negative correlation between the ERCCl and E-cadherin in the neoadjuvant chemotherapy group and the simple surgery group. Second, we showed that cisplatin-resistant A549 cells (A549/DDP) acquire EMT phenotype with high expression of drug-resistant proteins, P-gp and ERCC1. Knockdown of TGF-β1 may reverse EMT and significantly reduce the expression of P-gp and ERCC1. Moreover, A549/DDP cells become more sensitive to cisplatin. In summary, our results globally confirm a molecular and phenotypic association between chemoresistance and EMT of resistant tumour cells under a histological and cellular level. More importantly, silence of TGF-β1 may enhance sensitivity to cisplatin of A549/DDP through inducing the reversal of EMT and inhibiting the expression of resistance-associated proteins. Hence, inhibition of TGF-β1 could be considered as an effective strategy for eliminating resistant lung cancer.
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Authors | Jin Wang, Yunqing Chen, Fenggang Xiang, Min Li, Hong Li, Jinghua Chi, Keyu Ren |
Journal | Artificial cells, nanomedicine, and biotechnology
(Artif Cells Nanomed Biotechnol)
Vol. 46
Issue 7
Pg. 1505-1512
(Nov 2018)
ISSN: 2169-141X [Electronic] England |
PMID | 28918673
(Publication Type: Journal Article)
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Chemical References |
- Transforming Growth Factor beta1
- Cisplatin
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Topics |
- A549 Cells
- Carcinoma, Non-Small-Cell Lung
(pathology)
- Cisplatin
(pharmacology)
- Drug Resistance, Neoplasm
(drug effects, genetics)
- Epithelial-Mesenchymal Transition
(drug effects, genetics)
- Gene Knockdown Techniques
- Humans
- Lung Neoplasms
(pathology)
- Phenotype
- Signal Transduction
(drug effects)
- Transforming Growth Factor beta1
(genetics, metabolism)
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