Gene Expression Profiling and Pathway Network Analysis Predicts a Novel Antitumor Function for a Botanical-Derived Drug, PG2
Network analysis of PG2-enriched signature reveals the connection to immune function. (a) The subnetwork was composed of 87 genes, including graph-based clique and overexpressed genes. These genes were subsequently analyzed using CPDB pathway analysis. As indicated in this figure, several subnetworks were identified, including several immune-related signaling pathways, such as interleukin-mediated signaling, toll-like signaling, Trk receptor signaling, and the CTLA4 inhibitory pathway. Links represent a protein-protein interaction in the network. The size of each node is based on the number of links to other nodes. Nodes with upregulated and downregulated genes are colored in red and green, respectively. The depth of color indicates the gene expression level fold change. Several genes from PG2-enriched signature, represented by a black borderline on a node (e.g., STAT5A in CTLA4 inhibitory pathway), are not in the original pathway analysis but are included in the pathways of the subnetworks based on a literature survey. The network was visualized using Cytoscape 3.0 (http://www.cytoscape.org/). HL-60 cells were treated with different concentrations of PG2 for 6 hr. (b) PTPN11 and (c) NFKB2 mRNA was measured by Q-RT PCR and normalized to β-actin (). PG2 treatment alone drastically increased the production of IL-1β (d) and IL-6 (e) in human THP-1 macrophages () (; ; ).