Mechanism Study Of Pachymic Acid In Treating Gastric Cancer

Objective: Recent studies have showed that pachymic acid(PA)has a variety of pharmacological effects especially anticancer activities,and it's been found that PA could significantly inhibit most cancer cells.However,researches on identifying the potential targets of PA,especially its anti-tumor targets,and verifying these targets are still scarce.In this study,two systematic target prediction methods were used to predict the potential targets of PA,which were then mapped to the protein-protein interaction data to get the hub targets by constructing the molecular network.Verification of those hub targets and preliminary study on the mechanism of PA against gastric cancer were completed by means of experimental method.This will provide new ideas for seeking to novel targets of anticancer therapy and offer a certain experimental basis for the clinical application.Methods: Firstly,Chinese medicine molecule PA was chosen as our research object.Then,SysDT and WES these two target prediction models were respectively used to predict the potential targets of PA;The results of integrating potential targets and gastric cancer-related genes were subsequently mapped to the protein interaction database BioGRID and STRING,and we then used Cytoscape software to build molecular network to further select hub genes as possible anti-gastric cancer targets;Finally,target verification and anti-gastric cancer mechanism of action using both CETSA and western-blot technique were analyzed.Results:(1)By integrating the prediction results of the SysDT and WES models,43 potential targets of PA were selected.(2)1763 gastric cancer related genes were collected by GCgene database and gastric cancer biomarker.Then 15 seed targets were obtained by further integrating the potential targets of PA and gastric cancer related genes.After mapping these seed targets to the PPI network and analysing molecular action network,5 hub nodes/targets were finally determined based on the network topology parameters.(3)CETSA results showed that PA could bind to PPAR? in gastric cancer cells to change its thermal stability;Western-blot analysis showed that the expression of PPAR? protein was up-regulated with the treatment of PA in a concentration dependent manner;In addition,pretreatment GW9662,a PPAR? inhibitor,could influence the protein expression of Cyclin D1,Bcl-2,Bcl-x L,CDK4 and phosphorylation level of ERK1/2 and p38 caused by PA.Conclusion: PA can bind to PPAR? in gastric cancer cells,and further up-regulation of PPAR? protein expression.PPAR? is considered as an anti-gastric cancer target of PA.Gastric cancer therapy mechanism involved is likely to be through the control of some cycle,apoptosis-related factors and MAPK related proteins;these factors or proteins have been shown to play important roles in the occurrence and development of gastric cancer.The successful development of this study will provide a new strategy for the target prediction of Chinese medicine components,which will be of great guiding significance to study the anti-cancer mechanism and further promote the modernization of Chinese medicine development.