A Network Pharmacology-Based Analysis of Multi-Target, Multi-Pathway, Multi-Compound Treatment for Ovarian Serous Cystadenocarcinoma

Clin Drug Investig. 2018 Oct;38(10):909-925. doi: 10.1007/s40261-018-0683-8.


Background and objectives: Pharmacological control against ovarian serous cystadenocarcinoma has received increasing attention. The purpose of this study was to investigate multi-drug treatments as synergetic therapy for ovarian serous cystadenocarcinoma and to explore their mechanisms of action by the network pharmacology method.

Methods: Genes acting on ovarian serous cystadenocarcinoma were first collected from GEPIA and DisGeNET. Gene Ontology annotation, Kyoto Encyclopedia of Genes and Genomes pathway, Reactome pathway, and Disease Ontology analyses were then conducted. A connectivity map analysis was employed to identify compounds as treatment options for ovarian serous cystadenocarcinoma. Targets of these compounds were obtained from the Search Tool for Interacting Chemicals (STITCH). The intersections between the ovarian serous cystadenocarcinoma-related genes and the compound targets were identified. Finally, the Kyoto Encyclopedia of Genes and Genomes and Reactome pathways in which the overlapped genes participated were selected, and a correspondence compound-target pathway network was constructed.

Results: A total of 541 ovarian serous cystadenocarcinoma-related genes were identified. The functional enrichment and pathway analyses indicated that these genes were associated with critical tumor-related pathways. Based on the connectivity map analysis, five compounds (resveratrol, MG-132, puromycin, 15-delta prostaglandin J2, and valproic acid) were determined as treatment agents for ovarian serous cystadenocarcinoma. Next, 48 targets of the five compounds were collected. Following mapping of the 48 targets to the 541 ovarian serous cystadenocarcinoma-related genes, we identified six targets (PTGS1, FOS, HMOX1, CASP9, PPARG, and ABCB1) as therapeutic targets for ovarian serous cystadenocarcinoma by the five compounds. By analysis of the compound-target pathway network, we found the synergistic anti-ovarian serous cystadenocarcinoma potential and the underlying mechanisms of action of the five compounds.

Conclusion: In summary, latent drugs against ovarian serous cystadenocarcinoma were acquired and their target actions and pathways were determined by the network pharmacology strategy, which provides a new prospect for medicamentous therapy for ovarian serous cystadenocarcinoma. However, further in-depth studies are indispensable to increase the validity of this study.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / genetics
  • Cohort Studies
  • Cystadenocarcinoma, Serous / drug therapy*
  • Cystadenocarcinoma, Serous / genetics
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks / drug effects*
  • Gene Regulatory Networks / genetics
  • Humans
  • MCF-7 Cells
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Treatment Outcome