Zoledronic acid resensitises gefitinibresistant lung cancer cells by inhibiting the JAK/STAT3 signalling pathway and reversing epithelialmesenchymal transition.
Oncol Rep
; 45(2): 459-468, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33416163
ABSTRACT
Studies have shown that suppression of both the JAK/STAT3 pathway and epithelialmesenchymal transition (EMT) may overturn the resistance of nonsmall cell lung cancer (NSCLC) cells to gefitinib. Zoledronic acid (ZA) injection is used to treat and prevent multiple forms of osteoporosis, hypercalcemia and bone metastasisrelated complications of malignancy. Clinical research has shown that ZA may exert antitumour effects and delay the progression of NSCLC. In the present study, we investigated whether ZA combined with gefitinib could resensitise NSCLC cells to gefitinib in vitro and in vivo through inhibition of the JAK/STAT3 signalling pathway and EMT reversal. The results revealed that ZA potently increased the sensitivity of gefitinibresistant lung cancer cells to gefitinib. ZA decreased activation of JAK/STAT3 signalling and reversed EMT in the H1975 and HCC827GR cell lines. Furthermore, addition of IL6 to ZApretreated gefitinibresistant cell lines abrogated the effect of ZA and restored the cellular resistance to tyrosine kinase inhibitors. Finally, ZAbased combinatorial therapy effectively inhibited the growth of xenografts derived from gefitinibresistant cancer cells, which was correlated with the inhibition of the JAK/STAT3 signalling pathway and EMT reversal. In conclusion, ZA resensitised gefitinibresistant lung cancer cells through inhibition of the JAK/STAT3 signalling pathway and EMT reversal. The combination of ZA and gefitinib may be a promising therapeutic strategy to reverse gefitinib resistance and prolong the survival of patients with NSCLC.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Carcinoma Pulmonar de Células não Pequenas
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Resistencia a Medicamentos Antineoplásicos
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Ácido Zoledrônico
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Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article