Anti-Tumor Activity and Mechanism of Silibinin Based on Network Pharmacology and Experimental Verification
Peihai Li,
Dexu Wang,
Xueliang Yang,
Changyu Liu,
Xiaobin Li,
Xuanming Zhang,
Kechun Liu,
Yun Zhang,
Mengqi Zhang,
Changyun Wang,
Rongchun Wang
Affiliations
Peihai Li
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China
Dexu Wang
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China
Xueliang Yang
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China
Changyu Liu
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China
Xiaobin Li
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China
Xuanming Zhang
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China
Kechun Liu
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China
Yun Zhang
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China
Mengqi Zhang
Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Agro-Products Processing Technology of Shandong Province, Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, Jinan 250100, China
Changyun Wang
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Rongchun Wang
Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China
Silibinin is a flavonoid compound extracted from the seeds of Silybum marianum (L.) Gaertn. It has the functions of liver protection, blood-lipid reduction and anti-tumor effects. However, the potential molecular mechanism of silibinin against tumors is still unknown. This study aimed to assess the anti-tumor effects of silibinin in adenoid cystic carcinoma (ACC2) cells and Balb/c nude mice, and explore its potential mechanism based on network pharmacology prediction and experimental verification. A total of 347 targets interacting with silibinin were collected, and 75 targets related to the tumor growth process for silibinin were filtrated. Based on the PPI analysis, CASP3, SRC, ESR1, JAK2, PRKACA, HSPA8 and CAT showed stronger interactions with other factors and may be the key targets of silibinin for treating tumors. The predicted target proteins according to network pharmacology were verified using Western blot analysis in ACC2 cells and Balb/c nude mice. In the pharmacological experiment, silibinin was revealed to significantly inhibit viability, proliferation, migration and induce the apoptosis of ACC2 cells in vitro, as well as inhibit the growth and development of tumor tissue in vivo. Western blot analysis showed that silibinin affected the expression of proteins associated with cell proliferation, migration and apoptosis, such as MMP3, JNK, PPARα and JAK. The possible molecular mechanism involved in cancer pathways, PI3K-Akt signaling pathway and viral carcinogenesis pathway via the inhibition of CASP3, MMP3, SRC, MAPK10 and CDK6 and the activation of PPARα and JAK. Overall, our results provided insight into the pharmacological mechanisms of silibinin in the treatment of tumors. These results offer a support for the anti-tumor uses of silibinin.
