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

9 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

Salvia miltiorrhiza
Lung Neoplasms
Macrophages
Survival
STAT3 Transcription Factor
S-Phase Kinase-Associated Proteins
STAT Transcription Factors
Chemokine CCL2
Protein S
Chinese Traditional Medicine
National Health Programs
Coculture Techniques
dihydroisotanshinone I
Tumor Burden
Taiwan
Heterografts
Nude Mice
Therapeutics
Phosphorylation
Cell Proliferation

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells. / Wu, Ching Yuan; Cherng, Jong Yuh; Yang, Yao Hsu; Lin, Chun Liang; Kuan, Feng Che; Lin, Yin Yin; Lin, Yu Shih; Shu, Li Hsin; Cheng, Yu Ching; Liu, Hung Te; Lu, Ming Chu; Lung, Jthau; Chen, Pau Chung; Lin, Hui Kuan; Lee, Kuan Der; Tsai, Ying Huang.

In: Oncotarget, Vol. 8, No. 53, 2017, p. 90925-90947.

Research output: Contribution to journalArticle

Wu, CY, Cherng, JY, Yang, YH, Lin, CL, Kuan, FC, Lin, YY, Lin, YS, Shu, LH, Cheng, YC, Liu, HT, Lu, MC, Lung, J, Chen, PC, Lin, HK, Lee, KD & Tsai, YH 2017, 'Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells', Oncotarget, vol. 8, no. 53, pp. 90925-90947. https://doi.org/10.18632/oncotarget.18767
Wu, Ching Yuan ; Cherng, Jong Yuh ; Yang, Yao Hsu ; Lin, Chun Liang ; Kuan, Feng Che ; Lin, Yin Yin ; Lin, Yu Shih ; Shu, Li Hsin ; Cheng, Yu Ching ; Liu, Hung Te ; Lu, Ming Chu ; Lung, Jthau ; Chen, Pau Chung ; Lin, Hui Kuan ; Lee, Kuan Der ; Tsai, Ying Huang. / Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells. In: Oncotarget. 2017 ; Vol. 8, No. 53. pp. 90925-90947.
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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.",
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AU - Lin, Chun Liang

AU - Kuan, Feng Che

AU - Lin, Yin Yin

AU - Lin, Yu Shih

AU - Shu, Li Hsin

AU - Cheng, Yu Ching

AU - Liu, Hung Te

AU - Lu, Ming Chu

AU - Lung, Jthau

AU - Chen, Pau Chung

AU - Lin, Hui Kuan

AU - Lee, Kuan Der

AU - Tsai, Ying Huang

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