Effect and mechanism of EGCG on the inflammation related cancers

[Speaker] Xue-jun LI:1
[Co-author] Yilixiati Xiaokaiti:1
1:Dept. of Pharmacology, School of Basic Medical Sciences, Peking University, China

Inflammation plays a key role in the development and progression of cancers. Inflammation plays a key role in the development and progression of cancers. Inhibition of inflammation will prevent carcinogenesis. The neutrophils are important part of the pathways. Previously, we had found that curcumin upregulated alpha1-AT in cancer tissue, which is an endogenous inhibitor of neutrophil elastase(NE). Neutrophils and cancer cells are similar in character. Firstly, we used the C57 mouse bearing lung cancer model to observe the effect of EGCG on cancer. EGCG could prolong the survival time of cancer mice, reduce cancer volume. At a lower dose of EGCG showed a significantly reduction on the number of metastases in lung tissue and reduced the MPO activity as well. EGCG reversed the migration of NE-induced A549 cells, and inhibited the activity of NE in a dose-dependent manner. Using 2D-MS, we examined the differential protein profiling of EGCG in mouse cancer tissue and detected 12 differential proteins. Signal pathway enrichment analysis by ToppCluster indicated that the PI3K-Akt-mTOR signal pathway had the best network correlation. And the IRS-1, NE substrate; in the network had higher score than other proteins. EGCG up-regulated alpha1-AT and IRS-1, inhibited PI3K/Akt. Molecular docking and SPR results revealed that EGCG could dosedependently bind to NE. Our study shows that EGCG may have a certain inhibitory effect on inflammation-related cancers, and the mechanism is related to its up-regulation on alpha1-AT and its inhibition on NE, the both may be the potential drug target for cancer prevention and treatment.
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