Label-Free Quantitative Proteomics Analysis of the Sorafenib Resistance in HepG2 Cells

Drug resistance of sorafenib seriously affects the treatment effect of late-stage hepatocellular carcinoma (HCC) patients. However, the precise mechanism of resistance to sorafenib remains unclear. Therefore, to obtain a deep understand of sorafenib resistance mechanisms and find potential therapeut...

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Bibliographic Details
Published inJournal of analysis and testing Vol. 6; no. 3; pp. 308 - 317
Main Authors Wang, Zi-Xuan, Chu, Hong-Wei, Yang, Kai-Guang, Zhao, Bao-Feng, Liang, Zhen, Zhang, Li-Hua, Zhang, Yu-Kui
Format Journal Article
LanguageEnglish
Published Singapore Springer Nature Singapore 01.09.2022
Subjects
Analytical Chemistry
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Monitoring/Environmental Analysis
Original Paper
Hepatocellular carcinoma
Quantitative proteomics
Drug resistance
Sorafenib
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Summary:Drug resistance of sorafenib seriously affects the treatment effect of late-stage hepatocellular carcinoma (HCC) patients. However, the precise mechanism of resistance to sorafenib remains unclear. Therefore, to obtain a deep understand of sorafenib resistance mechanisms and find potential therapeutic targets are very important for improving the clinical prognosis of HCC patients. In this study, a label-free quantitative proteomics method was performed to investigate the proteins differentially expressed between HepG2 and the sorafenib-acquired resistance HepG2 (HepG2-R) cells. In total, 84 differential expressed proteins were identified between the two cell lines. Bioinformatics analysis results demonstrated the dysregulated metabolic processes have a significant impact on the drug resistance of HepG2-R cells. Among them, the expression of Microsomal glutathione S-transferase 1 (MGST1) in two cell lines was further confirmed by western blot method. Moreover, colony formation assay and trypan blue dye assay results revealed that MGST1 is closely connected with the sorafenib resistance of HepG2-R cells, and the knockdown of MGST1 increased the sensitivity of sorafenib resistance HepG2-R cells to sorafenib treatment. In conclusion, these results lay a foundation for deciphering the mechanism for HCC sorafenib resistance and present a possibility of MGST1 serving as a therapeutic target for the treatment of sorafenib resistance HCC.
ISSN:2096-241X
2509-4696
DOI:10.1007/s41664-021-00176-x