A New Strategy to Uncover the Anticancer Mechanism of Chinese Compound Formula by Integrating Systems Pharmacology and Bioinformatics.

Currently, cancer has become one of the major refractory diseases threatening human health. Complementary and alternative medicine (CAM) has gradually become an alternative choice for patients, which can be attributed to the high cost of leading cancer treatments (including surgery, radiotherapy, and chemotherapy) and the severe related adverse effects. As a critical component of CAM, traditional Chinese medicine (TCM) has increasing application in preventing and treating cancer over the past few decades. Huanglian Jiedu Decoction (HJD), a classical Chinese compound formula, has been recognized to exert a beneficial effect on cancer treatment, with few adverse effects reported. Nevertheless, the precise molecular mechanism remains unclear yet. In this study, we had integrated systems pharmacology and bioinformatics to explore the major active ingredients against cancer, targets for cancer treatment, and the related mechanisms of action. These targets were scrutinized using web-based Gene SeT Analysis Toolkit (WebGestalt), and 10 KEGG pathways were identified by enrichment analysis. Refined analysis of the KEGG pathways indicated that the anticancer effect of HJD showed a functional correlation with the p53 signaling pathway; moreover, HJD had potential therapeutic effect on prostate cancer (PCa) and small cell lung cancer (SCLC). Afterwards, genetic alterations and survival analysis of key targets for cancer treatment were examined in both PCa and SCLC. Our results suggested that such integrated research strategy might serve as a new paradigm to guide future research on Chinese compound formula. Importantly, such strategy contributes to studying the anticancer effect and the mechanisms of action of Chinese compound formula, which has also laid down the foundation for clinical application.