Molecular Mechanism by which Diosbulbin B Regulates the TP63 Gene in Triple-Negative Breast Cancer

Abstract

BackgroundDioscorea bulbifera L. is mainly used for antitumor therapy in clinical practice. Studies have shown that the drug-containing serum obtained from Dioscorea bulbifera L. induces the apoptosis and inhibits the proliferation of rat breast cancer cells. However, the main active compounds and the molecular mechanism in triple-negative breast cancer are still unclear.MethodsThe TCMSP, GeneCards, GEO and TCGA databases were used to identify genes that intersect the target genes of Dioscorea bulbifera L., active Dioscorea bulbifera L. components and triple-negative breast cancer targets, and Kaplan-Meier and GSEA methods were used to analyze the survival and pathway enrichment of the intersecting genes, respectively. Subsequently, in vitro experiments were performed for verification.ResultsA total of 14 active components were screened, and the targets of the active components were combined with triple-negative breast cancer-related targets and differentially expressed genes obtained from the GeneCards database. Three genes (CCNB1, PGR and TP63) are related to the anti-breast cancer effects of Dioscorea bulbifera L., and TP63 (P<0.05) is related to breast cancer survival. The GSEA showed that the TP63 gene is related to the apoptosis pathway, and TP63 gene analysis in the TCGA clinical database showed the greatest expression difference in triple-negative breast cancer. The in vitro experiments showed that diosbulbin B, the main antitumor compound in Dioscorea bulbifera L., may inhibit the proliferation and migration of MDA-MB-231 breast cancer cells and induce their apoptosis by promoting the expression of the TP63 gene.ConclusionThe present study fully elucidated the active components, potential targets and molecular mechanisms of Dioscorea bulbifera L. against triple-negative breast cancer and provided a new method for revealing the scientific basis and therapeutic mechanism of Chinese medicine in treating diseases.