Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells

Ching Yuan Wu, Jong Yuh Cherng, Yao Hsu Yang, Chun Liang Lin, Feng Che Kuan, Yin Yin Lin, Yu Shih Lin, Li Hsin Shu, Yu Ching Cheng, Hung Te Liu, Ming Chu Lu, Jthau Lung, Pau Chung Chen, Hui Kuan Lin, Kuan Der Lee, Ying Huang Tsai

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely used in the treatment of numerous cancers. However, its clinical effort and mechanism in the treatment of advanced lung cancer are unclear. In our study, the in vivo protective effort of danshen in patients with advanced lung cancer were validated using data from the National Health Insurance Research Database in Taiwan. We observed in vitro that dihydroisotanshinone I (DT), a bioactive compound in danshen, exerts anticancer effects through many pathways. First, 10 μM DT substantially inhibited the migration ability of lung cancer cells in both macrophage and macrophage/lung cancer direct mixed coculture media. Second, 10 μM DT repressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3), the protein expression of S-phase kinase associated protein-2 (Skp2), and the mRNA levels of STAT3-related genes, including chemokine (C-C motif) ligand 2 (CCL2). In addition, 10 μM DT suppressed the macrophage recruitment ability of lung cancer cells by reducing CCL2 secretion from both macrophages and lung cancer cells. Third, 20 μM DT induced apoptosis in lung cancer cells. Furthermore, DT treatment significantly inhibited the final tumor volume in a xenograft nude mouse model. In conclusion, danshen exerts protective efforts in patients with advanced lung cancer. These effects can be attributed to DT-mediated interruption of the cross talk between lung cancer cells and macrophages and blocking of lung cancer cell proliferation.

Original languageEnglish
Pages (from-to)90925-90947
Number of pages23
JournalOncotarget
Volume8
Issue number53
DOIs
Publication statusPublished - 2017

    Fingerprint

Keywords

  • CCL2
  • Dihydroisotanshinone I
  • Lung cancer
  • Macrophage
  • Skp2

ASJC Scopus subject areas

  • Oncology

Cite this

Wu, C. Y., Cherng, J. Y., Yang, Y. H., Lin, C. L., Kuan, F. C., Lin, Y. Y., Lin, Y. S., Shu, L. H., Cheng, Y. C., Liu, H. T., Lu, M. C., Lung, J., Chen, P. C., Lin, H. K., Lee, K. D., & Tsai, Y. H. (2017). Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells. Oncotarget, 8(53), 90925-90947. https://doi.org/10.18632/oncotarget.18767