Integrating network pharmacology and experimental verification to investigate the pharmacological mechanisms of Buzhong Yiqi decoction in the treatment of non-small cell lung cancer

Chem Biol Drug Des. 2024 Jan;103(1):e14414. doi: 10.1111/cbdd.14414.

Abstract

Among all types of cancers, non-small cell lung cancer (NSCLC) exhibits the highest mortality rate with a five-year survival rate below 17% for patients. The Buzhong Yiqi decoction (BZYQD), traditional Chinese medicine (TCM) formula, has been reported to exhibit clinical efficacy in the treatment of NSCLC. Nevertheless, the underlying molecular mechanism remains elusive. This study aimed to assess the mechanistic actions exerted by BZYQD against NSCLC using network pharmacological analysis and experimental validation. The public databases were searched for active compounds in BZYQD, their potential targets, and NSCLC-related targets. The protein-protein interaction (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the core targets and signaling pathways of BZYQD against NSCLC. After screening, this study validated the results of predictions through in vitro experiments and public databases. We found 192 common targets between BZYQD and NSCLC. KEGG analysis showed that the anti-NSCLC effects of BZYQD were mediated through the PI3K-AKT signaling pathway. The results of in vitro experiment indicated that BZYQD could inhibit cell viability and proliferation of A549 and H1299 cells apart from inducing cell apoptosis. In addition, western blot results substantiated that BZYQD could treat NSCLC by inhibiting the activation of the PI3K-AKT signaling pathway. The current study investigated the pharmacological mechanism of BZYQD against NSCLC via network pharmacology and in vitro analyses. Overall, the results revealed that BZYQD could be a promising therapeutic agent for the treatment of NSCLC in the future. Still, more experimental investigations are needed to confirm the applicability of BZYQD for clinical trials.

Keywords: Buzhong Yiqi decoction; PI3K-AKT signaling pathway; experimental verification; network pharmacology; non-small cell lung cancer.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Drugs, Chinese Herbal* / pharmacology
  • Humans
  • Lung Neoplasms* / drug therapy
  • Molecular Docking Simulation
  • Network Pharmacology
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt

Substances

  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Drugs, Chinese Herbal