Research Papers:

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 and Ying-Huang Tsai _

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Oncotarget. 2017; 8:90925-90947. https://doi.org/10.18632/oncotarget.18767

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Ching-Yuan Wu1,2, Jong-Yuh Cherng3, Yao-Hsu Yang1,2, Chun-Liang Lin4,5, Feng-Che Kuan6, Yin-Yin Lin1, Yu-Shih Lin7, Li-Hsin Shu1, Yu-Ching Cheng1, Hung Te Liu1, Ming-Chu Lu6, Jthau Lung8, Pau-Chung Chen9,17, Hui Kuan Lin10,11,12,13, Kuan-Der Lee6,16 and Ying-Huang Tsai14,15

1Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

2School of Chinese medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan

3Department of Chemistry and Biochemistry, National Chung Cheng University, Taiwan

4Departments of Nephrology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

5Kidney and Diabetic Complications Research Team (KDCRT), Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

6Department of Hematology and oncology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

7Department of Pharmacy, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

8Department of Medical Research and Development, Chang Gung Memorial Hospital, Chiayi branch, Taiwan

9Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan

10Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

11Department of Cancer Biology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC, USA

12Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

13Department of Biotechnology, Asia University, Taichung, Taiwan

14Division of Pulmonary and Critical Care Medicine of Chang Gung Memorial Hospital, Chiayi, Taiwan, Department of Respiratory Therapy, Chang Gung University, Taoyuan, Taiwan

15Chang-Gung University College of Medicine, Taoyuan, Taiwan

16Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taiwan

17Department of Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

Correspondence to:

Ying-Huang Tsai, email: [email protected]

Ching-Yuan Wu, email: [email protected]

Keywords: dihydroisotanshinone I, macrophage, lung cancer, Skp2, CCL2

Received: February 15, 2017     Accepted: June 10, 2017     Published: June 28, 2017


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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