Conclusion
AGK levels were increased in paclitaxel-resistant NPC cells. AGK activates JAK2/STAT3 signalling, thus promoting FOXM1 transcription and eventually enhancing the drug resistance of NPC cells.
Methods
MTT assay was employed to determine the IC50 of paclitaxel in NPC cells after different treatments. Flow cytometry assays were employed to evaluate cell apoptosis. RT-qPCR and Western blot assays were used to detect alterations in mRNA and protein expression, respectively. Luciferase assays and chromatin immunoprecipitation (ChIP) assays were used to determine the relationship between and the regulatory effect of STAT3 on the promoter of FOXM1.
Objective
Drug resistance is an important factor that impedes the treatment of nasopharyngeal cancer (NPC). Acylglycerol kinase (AGK) has been found to be overexpressed in NPC and correlates with poor prognosis. Our objective was to demonstrate the effect of AGK on paclitaxel resistance in NPC and determine the underlying mechanisms.
Results
AGK was elevated in paclitaxel-resistant NPC cells, and knockdown of AGK suppressed the resistance of CNE1-TR and CNE2-TR cells to paclitaxel. Moreover, upregulation of FOXM1 rescued the effects of AGK knockdown. Furthermore, the JAK2/STAT3 signalling pathway was overactivated in CNE1-TR and CNE2-TR cells, and knockdown of AGK suppressed JAK2/STAT3 signalling. STAT3 was verified to bind to and activate the promoter region of FOXM1. An in vivo tumour xenograft assay also verified that AGK knockdown inhibited tumour growth and mitigated paclitaxel resistance by regulating the JAK2/STAT3/FOXM1 axis.