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已发表论文
运用网络药理学、生物信息学分析及实验验证探究加味苇茎汤治疗非小细胞肺癌的作用机制
Authors Xu B, Yu Y, Zhang J, Jiang B , Yan L, Chen S, Hu L , Miao Q, Qi Y
Received 31 January 2025
Accepted for publication 19 September 2025
Published 25 September 2025 Volume 2025:19 Pages 8711—8743
DOI https://doi.org/10.2147/DDDT.S516745
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Anastasios Lymperopoulos
Bo Xu,1,2,* Yihan Yu,3,* Jixian Zhang,3,* Bo Jiang,4 Le Yan,4 Saili Chen,5 Linling Hu,4 Qing Miao,1 Yu Qi4,6
1Department of Pulmonary Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Postdoctoral Mobile Workstation, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Department of Pulmonary Medicine, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, People’s Republic of China; 4College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China; 5College of Clinical Medicine, Hubei University of Science and Technology, Xianning, People’s Republic of China; 6Hubei Shizhen Laboratory, Wuhan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Qing Miao, Department of Pulmonary Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email miaoqing55@sina.com Yu Qi, College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China, Email qy13871199637@163.com
Purpose: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. While Qianjin Weijin Decoction is widely used in China for lung cancer treatment, Jiawei Qianjin Weijin Decoction (JWWJD), a modified version, has shown enhanced anti-metastatic effects. However, its active components and underlying mechanisms remain unclear.
Methods: The effect of JWWJD against NSCLC was evaluated in vitro and in vivo, and the mechanisms were identified in combination with transcriptomics. Network pharmacology and bioinformatics were used to construct an anti-NSCLC prognostic model with JWWJD. The correlation between the expression of the prognostic gene and clinicopathological features was evaluated. The main active components of JWWJD were identified by LC-MS/MS and its anticancer effect and mechanism were investigated in vitro and in vivo.
Results: JWWJD-containing serum significantly suppressed cell proliferation and migration, and induced apoptosis in NCI-A549 and NCI-H23 cells. Among different concentrations tested, 20% drug-containing serum showed the most potent inhibitory effect on NSCLC progression (all P-values < 0.05). In a BALB/c-nu mouse xenograft model, oral administration of high-dose JWWJD reduced tumor volume by 27.76% compared to control (P < 0.001). Transcriptomic analysis revealed that JWWJD treatment led to significant downregulation of SPP1 (Fold Change = 0.687, FDR < 0.05), a gene highly associated with poor prognosis in NSCLC patients. Using LC-MS/MS, curcumol was identified as the key active component in JWWJD. Molecular studies demonstrated that curcumol directly binds to SPP1 with strong affinity (KD = 4.55× 10− 6 M), downregulates its expression, and inhibits NSCLC cell migration and invasion. In vivo experiments showed that curcumol reduced tumor volume by 24.88% (P < 0.001).
Conclusion: Our study, integrating transcriptomics, bioinformatics, LC-MS/MS, and experimental validation, revealed that JWWJD alleviates NSCLC metastasis by directly targeting SPP1. JWWJD and its active compound curcumol show promise as alternative therapies for NSCLC patients.
Keywords: Jiawei Weijin decoction, non-small cell lung cancer, SPP1, curcumol, metastasis
1Department of Pulmonary Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Postdoctoral Mobile Workstation, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Department of Pulmonary Medicine, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, People’s Republic of China; 4College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China; 5College of Clinical Medicine, Hubei University of Science and Technology, Xianning, People’s Republic of China; 6Hubei Shizhen Laboratory, Wuhan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Qing Miao, Department of Pulmonary Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email miaoqing55@sina.com Yu Qi, College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China, Email qy13871199637@163.com
Purpose: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. While Qianjin Weijin Decoction is widely used in China for lung cancer treatment, Jiawei Qianjin Weijin Decoction (JWWJD), a modified version, has shown enhanced anti-metastatic effects. However, its active components and underlying mechanisms remain unclear.
Methods: The effect of JWWJD against NSCLC was evaluated in vitro and in vivo, and the mechanisms were identified in combination with transcriptomics. Network pharmacology and bioinformatics were used to construct an anti-NSCLC prognostic model with JWWJD. The correlation between the expression of the prognostic gene and clinicopathological features was evaluated. The main active components of JWWJD were identified by LC-MS/MS and its anticancer effect and mechanism were investigated in vitro and in vivo.
Results: JWWJD-containing serum significantly suppressed cell proliferation and migration, and induced apoptosis in NCI-A549 and NCI-H23 cells. Among different concentrations tested, 20% drug-containing serum showed the most potent inhibitory effect on NSCLC progression (all P-values < 0.05). In a BALB/c-nu mouse xenograft model, oral administration of high-dose JWWJD reduced tumor volume by 27.76% compared to control (P < 0.001). Transcriptomic analysis revealed that JWWJD treatment led to significant downregulation of SPP1 (Fold Change = 0.687, FDR < 0.05), a gene highly associated with poor prognosis in NSCLC patients. Using LC-MS/MS, curcumol was identified as the key active component in JWWJD. Molecular studies demonstrated that curcumol directly binds to SPP1 with strong affinity (KD = 4.55× 10− 6 M), downregulates its expression, and inhibits NSCLC cell migration and invasion. In vivo experiments showed that curcumol reduced tumor volume by 24.88% (P < 0.001).
Conclusion: Our study, integrating transcriptomics, bioinformatics, LC-MS/MS, and experimental validation, revealed that JWWJD alleviates NSCLC metastasis by directly targeting SPP1. JWWJD and its active compound curcumol show promise as alternative therapies for NSCLC patients.
Keywords: Jiawei Weijin decoction, non-small cell lung cancer, SPP1, curcumol, metastasis