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. 2022 Oct 13;13:972825. doi: 10.3389/fphar.2022.972825

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Copyright © 2022 Ma, Wu, Bai, Wang, Ma, Guo, Liu, Leng, Kong and Zhang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Targets of licoricidin inhibiting the growth of gastric cancer cells were identified by the quantitative proteomics research strategy of TMT labeling. MGC-803 cells were treated with 10 μM of licoricidin or untreated as a control. After protein extraction, mass spectrometry identification, and database search, the differential proteins were screened out. Independent experiments were repeated three times. (A) Statistics of the protein identification results. (B) Volcano plot of differentially expressed proteins. The significantly downregulated proteins are marked in blue (FC < 0.83 and p < 0.05), and strikingly up-regulated proteins are marked in red (FC > 1.2 and p < 0.05), while non-differentiated proteins are plotted in gray. (C) Hierarchical cluster classified proteins with differential expression and were displayed on the heatmap. The expression levels of significantly different proteins were normalized using the log2 method and revealed in different colors. The red and blue parts represent significantly upregulated and downregulated proteins, respectively. Domain enrichment (D) and GO molecular function enrichment (E) of differentially expressed proteins were analyzed by Fisher’s exact test. The closer to red color, the higher the enrichment degree. (F) Increased or decreased ICMT in different cancers was compared with that of paired normal tissues by gene expression profiling interactive analysis. (G) ICMT expression in different tumor types with or without paracancer determined by TIMER. (H) Three-dimensional structure of ICMT (PDB code:5V7P) was downloaded from Protein Data Bank (https://www.rcsb.org/3d-view/5V7P). (I) Licoricidin bound to the active site (TYR131 residue) of ICMT via forming a hydrogen bond in the molecular docking mode. The docking score was −9.165. (J) Expression level of ICMT in vitro was demonstrated by Western blot assay and normalized by β-tubulin for quantitative analysis. Independent experiments were repeated three times. Values are expressed as mean ± SD, **p < 0.01 and ***p < 0.001. LCD, licoricidin. 5-FU, 5-fluorouracil.