Résumé
Objective:The methods of network pharmacology were adopted to predict Multi-component Chinese Medicine （MCCM） with anti-tumor activity from Shuanghuanglian （SHL）. Furthermore， the pharmaceutical activity of CT26 colon cancer was verified in vitro and in vivo. Method:Based on the Traditional Chinese Medicine Systems Pharmacology Database （TCMSP）， the Handbook of Active Components Analysis of Traditional Chinese Medicine， the Drugbank database， the Reactome database， and the Human protein reference database （HPRD）， the protein-protein interactions network （PPI） and the drug target network were built and resolved. The data was mined to discover the pharmacological effect. The anti- tumor activity of components from SHL was determined based on the nearest distance rule between the compounds and the nodes of network. And then， the anti-tumor effect of the MCCM was verified in vitro and in vivo. Result:The 3 combined compounds， baicalin， forsythoside A and chlorogenic acid with the anti-tumor activity from SHL were predicted and discovered. The verification results showed that the combination of baicalin-forsythoside A-chlorogenic acid could significantly inhibit the cell proliferation and migration compared with the control group in vitro （P<0.01）. Among CT26 bearing mice， the tumor volume and weight were significantly decreased after the combined administration of baicalin-forsythoside A-chlorogenic acid compared with the model group in vivo （P<0.01）. Conclusion:By the methods of network pharmacology， the anti-tumor activities of component of from SHL were discovered. According to the verification in vitro and in vivo， the combination of baicalin-forsythoside A-chlorogenic acid could play better anti-CT26 tumor activity.
Résumé
Carnosol has been proved to have anti-breast cancer effect in previous research. But its ER subtype's specific regulation and mediation mechanisms remain unclear. The aim of this study is to observe the effect of carnosol on cell proliferation and its estrogen receptor α and β's specific regulation and mediation mechanisms with ER positive breast cancer T47D cell. With estrogen receptor α and β antagonists MPP and PHTPP as tools, the MTT cell proliferation assay was performed to observe the effect of carnosol on T47D cell proliferation. The changes in the T47D cell proliferation cycle were detected by flow cytometry. The effect of carnosol on ERα and ERβ expressions of T47D cells was measured by Western blot. The findings showed that 1 x 10(-5)-1 x 10(-7) mol x L(-1) carnosol could significantly inhibit the T47D cell proliferation, which could be enhanced by MPP or weakened by PHTPP. Meanwhile, 1 x 10(-5) mol x L(-1) or 1 x 10(-6) mol x L(-1) carnosol could significantly increase ERα and ERβ expressions of T47D cells, and remarkably increase ERα/ERβ ratio. The results showed that carnosol showed the inhibitory effect on the proliferation of ER positive breast cancer cells through target cell ER, especially ERβ pathway. In the meantime, carnosol could regulate expressions and proportions of target cell ER subtype ERα and ERβ.