Published online Feb 15, 2023. doi: 10.4251/wjgo.v15.i2.286
Peer-review started: September 8, 2022
First decision: November 12, 2022
Revised: November 23, 2022
Accepted: January 5, 2023
Article in press: January 5, 2023
Published online: February 15, 2023
Processing time: 159 Days and 10.9 Hours
Cancerous inhibitor of protein phosphatase 2A (CIP2A) plays a key role in various types of tumors, which may be related to the resistance of gastric cancer (GC) cells to oxaliplatin.
The mechanism of drug resistance in gastric cancer needs to be further studied, and CIP2A expression in GC cells and the mechanism of oxaliplatin resistance may be a breakthrough.
To explore the expression of the CIP2A in human GC cells and its correlation with oxaliplatin resistance.
Immunohistochemistry was used to examine CIP2A expression in GC tissues and adjacent normal tissues. CIP2A gene expression in GC cell lines was reduced using small interfering RNA. After confirming the silencing efficiency, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium and flow cytometry assays were used to evaluate cell proliferation and apoptosis, respectively, caused by oxaliplatin treatment. Further, the key genes and protein changes were verified using real-time quantitative reverse transcription PCR and Western blotting, respectively, before and after intervention. For bioinformatics analysis, we used the R software and Bioconductor project. For statistical analysis, we used GraphPad Prism 6.0 and the Statistical Package for the Social Sciences software version 20.0.
High CIP2A expression was associated with tumor size, T stage, lymph node metastasis, Tumor Node Metastasis stage, and poor prognosis. CIP2A knockdown inhibited cell proliferation and significantly increased the susceptibility of GC cells to oxaliplatin. CIP2A regulated the phosphorylation of protein kinase B, and chemical inhibition of the protein kinase B signaling pathway was significantly associated with increased sensitivity to oxaliplatin.
CIP2A expression was closely related to chemotherapy resistance of GC cells. The protein kinase B signaling pathway was correlated with CIP2A-enhanced chemoresistance of human GC cells to oxaliplatin.
Regulation of CIP2A expression may be one of the key points in the treatment of GC chemotherapy resistance.