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
de 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protocoles de polychimiothérapie antinéoplasique
/
Carcinome pulmonaire non à petites cellules
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Résistance aux médicaments antinéoplasiques
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Acide zolédronique
/
Tumeurs du poumon
Type d'étude:
Prognostic_studies
Limites:
Animals
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Female
/
Humans
Langue:
En
Journal:
Oncol Rep
Sujet du journal:
NEOPLASIAS
Année:
2021
Type de document:
Article