GSE124715
The Effect of Compound Kushen Injection on Cancer Cells: Integrated Identification of Candidate Molecular Mechanisms
Compound Kushen Injection (CKI) is a TCM fomula  has been in use in hospitals in China for over twenty years for the integrated treatment of cancer.There is little evidence based medicine supporting such complex mixture. Because TCM preparations are often combinations of multiple herbs containing hundreds of compounds, they have been difficult to study.  The development of high throughput -omics methods has allowed better characterization of TCM. We have applied high-throughput transcriptome data in two additional cancer cell lines and integrated our differential expression results across cell lines to identify a reduced set of differentially expressed (DE) candidate genes as well as a reproducible set of candidate pathways that are perturbed by CKI. In our results,CKI induced cell-cycle arrest and apoptosis. We identified 363 core candidate genes that were associated with cell cycle, apoptosis, DNA replication/repair and various cancer pathways. Of these, 7 are known to be clinically relevant to cancer diagnosis or therapy and 14 are cell cycle regulators, and most of these 21 candidates are downregulated by CKI. Comparison of our core candidate genes to a database of plant medicinal compounds and their effects on gene expression identified one-to-one, one-to-many and many-to-many regulatory relationships between compounds in CKI and DE genes.By identifying a number of promising candidate pathways and genes associated with CKI based on our transcriptome based analysis, we have shown this type of approach is useful for the systematic analysis of molecular changes resulting from complex mixtures of bioactives in the context of cancer therapy. Overall design: High-depth paired-end RNA-seq from HEPG2 and MDA-MB-231 cell lines. Each sample contains 3 biological replicates.