RESUMEN
Compound Kushen injection (CKI) has been extensively used in treating breast cancer (BC). However, the molecular mechanism remains unclear. In this study, 16 active compounds of CKI were obtained from 3 articles for target prediction. Then, a compound-predicted target network and a compound-BC target network were conducted by Cytoscape 3.6.1. The gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the DAVID database. The binding energy between the key targets of CKI and the active compounds was studied by molecular docking. As a result, 16 active compounds of CKI were identified, corresponding to 285 putative targets. The key targets of CKI for BC are HSD11B1, DPP4, MMP9, CDK1, MMP2, PTGS2, and CA14. The function enrichment analysis obtained 13 GO entries and 6 KEGG pathways, including bladder cancer, cancer pathways, chemical carcinogenesis, estrogen signaling pathway, TNF signaling pathway, and leukocyte transendothelial migration. The result of molecular docking indicated that DPP4 had strong binding activity with matrine, alicyclic protein, and sophoridine, and MMP9 had strong binding activity with adenine and sophoridine. In conclusion, the therapeutic effect of CKI on BC is based on the overall pharmacological effect formed by the combined effects of multiple components, multiple targets, and multiple pathways. This study provides a theoretical basis for further experimental research in the future.
RESUMEN
Background: Given the limitations of chemotherapy for the treatment of breast cancer (BC) and the wide exploration of Chinese herbal injections (CHIs), this network meta-analysis (NMA) was conducted to analyze the comparative efficacy and safety of nine CHIs combined with CF (Cyclophosphamide and 5-Fluorouracil) chemotherapy regimens in the treatment of BC. Methods: Several electronic databases were searched to identify randomized controlled trials (RCTs) from inception to January 6, 2020. RCTs were screened by pre-established eligibility criteria, and the quality of which was assessed using the Cochrane risk of bias tool. Outcomes such as the clinical effectiveness rate, performance status, peripheral hemogram, and detection of T-lymphocyte subsets were analyzed using the Winbugs 1.4.3 and Stata 13.0 software. Surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Cluster analysis was performed to compare the effect of CHIs between two or three different outcomes. Results: A total of 84 RCTs involving 7855 patients and nine CHIs were included. The results showed that compared to CF chemotherapy regimens alone, the ones injected along with Aidi, Shenmai, Shenqi Fuzheng, Kangai, Kanglaite, or Shengmai combined with CF can improve the clinical effectiveness rate. Aidi, Shenmai, Shenqi Fuzheng, Compound Kushen, Kangai, and Kanglaite injection combined with CF can improve the performance status. Shenqi Fuzheng injection was considered as a favorable choice for relieving adverse reactions. According to the results of cluster analysis, Aidi injection and Compound Kushen injection plus CF were more favorable for the clinical effectiveness rate and performance status. Conclusion: In conclusion, Shenqi Fuzheng, Compound Kushen, Aidi, and Kangai injection combined with CF chemotherapy regimen have more significant effects for patients with BC. However, more high-quality clinical RCTs, especialy which correctly use blinding and allocation concealment, are required to support the conclusions.