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
Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
School of Chinese medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Oncotarget. 2017 Jun 28;8(53):90925-90947. doi: 10.18632/oncotarget.18767. eCollection 2017 Oct 31.
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 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 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.
在传统中医中，丹参被广泛用于治疗多种癌症。然而，其在晚期肺癌治疗中的临床效果和机制尚不清楚。在我们的研究中，利用台湾国民健康保险研究数据库的数据验证了丹参对晚期肺癌患者的保护作用。我们观察到，丹参中的生物活性化合物二氢异丹参酮I（DT）通过多种途径发挥抗癌作用。首先，10 μM DT在巨噬细胞和巨噬细胞/肺癌直接混合共培养培养基中均显著抑制肺癌细胞的迁移能力。其次，10 μM DT抑制信号转导和转录激活因子3（STAT3）的磷酸化、S期激酶相关蛋白2（Skp2）的蛋白表达以及包括趋化因子（C-C基序）配体2（CCL2）在内的STAT3相关基因的mRNA水平。此外，10 μM DT通过减少巨噬细胞和肺癌细胞中CCL2的分泌来抑制肺癌细胞招募巨噬细胞的能力。第三，20 μM DT诱导肺癌细胞凋亡。此外，DT治疗显著抑制了异种移植裸鼠模型中的最终肿瘤体积。总之，丹参对晚期肺癌患者具有保护作用。这些作用可归因于DT介导的肺癌细胞与巨噬细胞之间的相互作用中断以及肺癌细胞增殖的阻断。
