Recognition of potential therapeutic role of 2‐hydroxy‐3‐methylanthraquinones in the treatment of gallbladder carcinoma: A proteomics analysis

Background

Gallbladder carcinoma (GBC), with early metastasis and high recurrence rates, is a enormous threat to health. As an anthraquinones monomer of traditional Chinese medicine Hedyotis diffusa, 2-hydroxy-3-methylanthraquinones (HMA) has been reported to inhibit the growth of several cancers. But in our preliminary study, HMA could only weakly induce GBC cell apoptosis.

Objective

To explore other possible mechanism underlying the inhibition effect of HMA on GBC, this proteomics analysis was performed.

Methods

A proteomics analysis was performed on one GBC cell line bought from the China Life Science Cell Bank. Several computational techniques were merged to develop analysis for those differently expressed proteins. A comparative protein-protein interaction network analysis was carried out among the differently expressed proteins to identify the proteins potentially inhibiting GBC. Thus, a GO and KEGG analysis was performed to identify the signaling pathways underlying a potential therapeutic role for HMA.

Results

A total of 285 proteins were affected by HMA, including 187 up-regulated and 98 down-regulated. The subcellular localization of differently expressed proteins were identified, including 142 in nuclear, 67 in cytoplasm, 67 in extracellular matrix, 46 in plasma membrane, 13 in mitochondrion, 3 in lysosome and 1 in cytoskeleton. HMA could regulate EGFR, FN1, PLG, PLAUR, LAMA3, HRG, THBS1, PLAT, KNG1, ENAM, SERPINE1, ECM1, interleukin-8 and trypsin in GBC. Most of the regulated proteins involve in cell migration. Pathways including PI3K-Akt, Wnt, HIF-1, focal adhesion, microRNAs were regulated by HMA.

Conclusion

HMA was shown to be an inhibition agent for GBC development, and this analysis would contribute to the development of new anti-GBC drugs.

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