The Core Mechanism of Yiqi Yangjing Decoction Inhibiting Nonsmall-Cell Lung Cancer

Background: Yiqi Yangjing prescription (YQYJ) is a traditional Chinese medicine prescription used for treating lung Cancer. It has a significant effect on enhancing efficacy, reducing toxic symptoms, and improving patients' physical well-being. The effective inhibitory effect on nonsmall-cell lung Cancer (NSCLC) has been demonstrated in vitro and in vivo. However, the mechanism of action and the material basis still remain unclear.

Methods: In this study, we explored this mechanism using network pharmacology, after which we explored the pharmacodynamics and the action mechanism of YQYJ using cell viability evaluation, plate clone formation assay, flow cytometry, real-time quantitative PCR, and Western blot.

Results: The enrichment results showed that there were 50 active components and 68 core targets related to YQYJ inhibiting NSCLC, including quercetin, luteolin, gamatin, kaempferol, heat shock protein HSP 90-alpha (HSP90AA1), cyclin-dependent kinase 2 (CDK2), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), and Others. Among them, quercetin and kaempferol revealed the best binding effect with core targets. Most importantly, YQYJ promoted A549 cells from the quiescent phase into the proliferative phase to enhance the sensitivity of A549 cells to YQYJ and inhibited the proliferation of A549 cells significantly (P < 0.05). The A549 cells were blocked in both S and G2/M phases while the Apoptosis ratio was increased. The proliferation score of A549 cells treated with YQYJ was significantly reduced compared to A549 cells in the proliferative phase (P < 0.05). This regulatory effect was related to the expression regulation of HSP90AA1, CDK2, STAT3, and phosphor-STAT3 (p-STAT3) by YQYJ, kaempferol, and quercetin.

Conclusion: Our results suggested that the inhibition of NSCLC via YQYJ had multicomponent and multitarget characteristics. Its core mechanism is related to the regulation of the cell cycle, proliferation, and Apoptosis of NSCLC. This study provides a direction and scientific basis for exploring the future mechanism of YQYJ for the treatment of NSCLC.