关键词: 乳腺癌, 复方山慈菇, MDA?MB?231细胞, 裸鼠移植瘤, 网络药理学

Abstract: Objective To investigate the inhibitory effect of compound cremastra appendiculata on the growth of human breast cancer MDA⁃MB⁃231 cell xenografts in nude mice and its potential mechanism. Methods The nude mice of model human breast cancer MDA⁃MB⁃231 cell xenografts were randomly divided into model group, doxorubicin (DOX) group, compound cremastra appendiculata ethanol extraction (CCAEE) high⁃dose group (1.8 g/kg) and CCAEE low⁃dose group (0.9 g/kg), with 5 mice in each group. After 21 days of continuous drug administration, the nude mice were sacrificed, and the tumor volume, tumor weight and tumor inhibition rate were calculated. The effective components of compound cremastra appendiculata and their corresponding targets were selected from the TCMSP 2.3 database, and the key targets were screened from the OMIM, GeneCards 5.14, DrugBank 5.1.10 and TTD databases.The protein⁃protein interaction (PPI) network of key targets was constructed by STRING 11.5 database. Then, the core targets were screened to establish the "drug⁃component⁃target" network and screen the core effective components. GO and KEGG enrichment analyses were performed using the Metascape 3.5 platform. Results Compared with the model group, after the 21 days treatment, the tumor volume and weight of the nude mice in DOX group, CCAEE high⁃dose group and low⁃dose group were significantly reduced (all P<0.05), and the tumor inhibition rates were 89.67%, 67.39% and 43.48%, respectively. 27 effective ingredients of compound cremastra appendiculata and 108 key targets for against breast cancer were obtained through a network pharmacological analysis, including 23 core targets (TP53, MAPK3, MAPK1, RELA, AKT1, FOS, ESR1, TNF, IL6, MAPK14, etc.) and 5 core  effective components (quercetin, kaempferol, β⁃sitosterol, 2⁃methoxy⁃9, 10⁃dihydro⁃4, 5⁃diol, and deoxypodophyllotoxin). GO and KEGG enrichment analyses indicated that compound cremastra appendiculata showed its anti⁃breast cancer effect mainly through the regulation of the biological processes such as hormone regulation and the signaling pathways such as PI3K⁃AKT and MAPK. Conclusions Compound cremastra appendiculata can inhibit the growth of human breast cancer xenograft, probably by acting on core targets such as TP53 and signaling pathways such as PI3K⁃AKT and MAPK through core effective ingredients such as quercetin and kaempferol.

Key words:  Breast cancer, Compound cremastra appendiculata, MDA?MB?231 cells, Cancer xenograft in nude mice, Network pharmacology