Xu Hao, Guo Ning Ning, Zhu Chen Ying, Ye Lin Yan, Yan Xing Yi, Liu Yong Qin, Zhang Ze Yan, Zhang Guangji, Hussain Liaqat
College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, P. R. China.
Inner Mongolia Medical University, Inner Mongolia, Hohhot 010110, P. R. China.
ACS Omega. 2024 Feb 2;9(6):7230-7238. doi: 10.1021/acsomega.3c09667. eCollection 2024 Feb 13.
Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from . High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.
二萜类丹参酮（DTs）是从……中提取的一种生物活性成分。高效液相色谱分析显示存在四种化合物，即丹参酮IIA、丹参酮I、隐丹参酮和二氢丹参酮。在本研究中，我们旨在提出DT抗肺癌作用的可能机制。为此，我们利用肺癌裸鼠模型和肺癌细胞系（PC9）来研究DT对肺癌的影响。我们采用免疫组织化学、酶联免疫吸附测定、苏木精和伊红染色以及免疫荧光来分析DT在抑制肺癌生长中的药理作用。结果表明，DT抑制肿瘤生长，在裸鼠模型中诱导细胞凋亡，并减少炎性细胞浸润。此外，DT抑制PC9肺癌细胞的生长、增殖和迁移。DT的作用机制不仅涉及直接抑制细胞增殖和迁移，还涉及改善肿瘤微环境。DT显著增加了重要的肠道紧密连接蛋白的表达，如闭合蛋白1（ZO-1）和闭合蛋白I。这种上调有助于加强肠道黏膜屏障，从而减少脂多糖（LPS）通过肠道的细胞旁转运。因此，LPS水平的降低导致NF-κB表达的抑制和巨噬细胞极化的下调，如CD68表达的降低所示。总之，本研究证实DT通过调节巨噬细胞极化和抑制LPS相关免疫反应来改善炎性肿瘤微环境，从而具有抗肺癌特性。这些结果为DT抗肺癌作用机制提供了新的见解。
