Abstract
As a Chinese herb medicine (CHM), Bo-Er-Ning capsule (BENC) has been approved in China for adjuvant treatment of cancer, but the particular therapeutic effect of BENC on gastric cancer (GC) has yet to be evaluated. In this study, we implemented an efficacy-driven approach by directly starting the study with a randomized clinical trial to assess the add-on therapeutic effect of BENC on advanced GC patients. Our results showed that the addition of BENC to chemotherapy resulted in higher Karnofsky performance scores and better 3-year overall survival, compared to those treated with the conventional chemotherapy regimen. Subsequently, we explored the mechanism of BENC action on GC cells in the assistance of BATMAN-TCM, the first online bioinformatics analysis tool designed especially for the mechanism study of CHM, by which we identified 263 candidate protein targets of BENC involved in GC treatment. The further enrichment analysis suggested that BENC treatment affected a diversity of biological processes of GC cells, such as cell proliferation, cell cycle and apoptosis, which were further validated in the following in vitro and in vivo assays, indicating such a bioinformatics-assisted approach was feasible and powerful to CHM mechanism study. Thus, as exemplified by BENC, we provided an efficacy-driven and bioinformatics-assisted strategy for CHM research, which may help promote the discovery and application of novel CHM drugs on patients with refractory diseases.