J Gynecol Oncol.  2020 Apr;31(3):e28. 10.3802/jgo.2020.31.e28.

Quantitative analysis of proteins related to chemoresistance to paclitaxel and carboplatin in human SiHa cervical cancer cells via iTRAQ

• He Y
• Han SB
• Geng YN
• Yang SL
• Wu YM

• KMID: 2500479
• DOI: http://doi.org/10.3802/jgo.2020.31.e28

Abstract

Objective
This study aimed to identify proteins related to paclitaxel and carboplatin chemoresistance in cervical cancer.
Methods
Quantitative proteomic analysis was performed on normal SiHa cells and those treated with paclitaxel and carboplatin for 14 days, with isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify related processes and differentially expressed proteins.
Results
A total of 67 and 96 differentially expressed proteins were identified in the paclitaxel- and carboplatin- treated groups, respectively. GO and KEGG enrichment analyses identified 53 (43 upregulated and 10 downregulated) and 85 differentially expressed proteins (70 upregulated and 15 downregulated) in the paclitaxel- and carboplatin-treated groups, respectively. The cell counting kit-8 results revealed that APOA1 was overexpressed in both the paclitaxel- and carboplatin- resistant SiHa cells compared with the control cells. Immunohistochemistry showed that APOA1 was highly expressed in the paclitaxel- and carboplatin- resistant squamous cell carcinoma of the cervix.
Conclusion
This study is the first to use iTRAQ to identify paclitaxel- and carboplatin- resistance proteins in cervical cells. We identified several proteins previously unassociated with paclitaxel and carboplatin resistance in cervical cancer, thereby expanding our understanding of paclitaxel and carboplatin resistance mechanisms. Moreover, these findings indicate that the APOA1 protein could serve as a potential marker for monitoring and predicting paclitaxel and carboplatin resistance levels.

Keyword

Antineoplastic Agent Resistance; Paclitaxel; Carboplatin; Cervical Cancer; Protein Microarray Analysis