Chaperonin containing TCP1 subunit 3 (CCT3) promotes cisplatin resistance of lung adenocarcinoma cells through targeting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway

ABSTRACT

Cisplatin resistance remains a major obstacle to effective chemotherapies for non-small cell lung cancer (NSCLC). Chaperonin containing TCP1 subunit 3 (CCT3) has been extensively investigated in various cancers, but not in the context of drug resistance. In the present study, we aimed to investigate the role of CCT3 in cisplatin resistance of lung adenocarcinoma (LUAD) cells. By surveying the Gene Expression Profiling Interactive Analysis (GEPIA) website, we found CCT3 expression to be up-regulated in NSCLCs, which correlated with the poor prognosis of LUAD patients. Furthermore, both mRNA and protein levels of CCT3 were upregulated in the cisplatin-resistant A549/DDP cells compared to the cisplatin-sensitive A549 cells. Importantly, upon cisplatin treatment, short hairpin RNA (shRNA)-mediated CCT3 knockdown significantly inhibited the proliferation, invasion and migration of A549/DDP cells, and induced significant G2/M cell cycle arrest and apoptosis in A549/DDP cells. Moreover, CCT3 knockdown significantly weakened the tumorigenicity of the cisplatin-treated A549/DDP cells in vitro and in vivo. Finally, CCT3 knockdown re-sensitized A549/DDP cells to cisplatin through inhibiting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway. In conclusion, our results demonstrated that CCT3 could promote cisplatin resistance of LUAD cells via activating the JAK2/STAT3 pathway, indicating that CCT3 may be a novel molecular target for overcoming cisplatin resistance in LUAD patients.

KEYWORDS:

• CCT3
• cisplatin resistance
• non-small cell lung carcinomas
• pathway

Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Authors’ contributions

DN Xu conducted the experiments and drafted the manuscript. YD L designed the study and revised the manuscript. JZ Z, HM S, YL P and CC Y collected and analyzed the data. All authors read and approved the final manuscript.

Disclosure statement

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

The study was approved by Ethics committee of the First Affiliated Hospital of Hainan Medical College.

Additional information

Funding

The work was funded by Basic and applied research program of Hainan Province (Provincial Natural Science Foundation) (Youth Fund Project) [NO. 819QN369].