Cinnamomi Ramulus inhibits the growth of colon cancer cells via Akt/ERK signaling pathways

桂枝通过Akt/ERK信号通路抑制结肠癌细胞生长

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作者:Boyu Pan #, Yafei Xia #, Zilu Gao #, Gang Zhao, Liangjiao Wang, Senbiao Fang, Liren Liu, Shu Yan

Background

Colon cancer (CC) ranks the second highest mortality rate among malignant tumors worldwide, and the current mainstream treatment regimens are not very effective. The unique efficacy of Chinese herb medicine (CHM) for cancer has recently attracted increasing attention. Cinnamomi Ramulus (CR), as a classic CHM, has been widely used in the treatment of a variety of diseases for hundreds of years in China, but its specific pharmacological mechanism against CC needs to be fully evaluated.

Conclusions

Our results show that CR as well as its active component taxifolin holds great potential in treatment of CC.

Methods

TCMSP and China National Knowledge Infrastructure database were utilized to predict the candidate ingredients of CR, and TCMSP and SwissTargetPrediction database were also employed to predict the drug targets of the candidate ingredients from CR. We subsequently evaluated the therapeutic effect of CR by orally administrating it on CC-bearing mice. Next, we further identified the potential CC-related targets by using Gene Expression Omnibus (GEO) database. Based on these obtained targets, the drug/disease-target PPI networks were constructed using Bisogenet plugin of Cytoscape. The potential core therapeutic targets were then identified through topological analysis using CytoNCA plugin. GO and KEGG enrichment analyses were performed to predict the underlying mechanism of CR against CC. Furthermore, these in silico analysis

Results

In this study, we firstly found that CR has potential therapeutic effect on cancer. Then, oral administration of CR could inhibit the growth of CC cells in C57BL/6 mice, while inhibiting the viability and motility of CC cells in vitro. We obtained 111 putative core therapeutic targets of CR. Subsequent enrichment analysis on these targets showed that CR could induce apoptosis and cell cycle arrest in CC cells by blocking Akt/ERK signaling pathways, which was further experimentally verified. We identified 5 key components from the crude extract of CR, among which taxifolin was found most likely to be the key active component against CC. Conclusions: Our results show that CR as well as its active component taxifolin holds great potential in treatment of CC.

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