Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, China.
State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Parmaceutical Co. Ltd., Lianyungang, China.
Phytomedicine. 2020 Dec;79:153326. doi: 10.1016/j.phymed.2020.153326. Epub 2020 Sep 1.
Lung cancer is the most common and mortal cancer worldwide. Rhodiola rosea L. (RR), a well-known traditional Chinese medicine (TCM), has been turned out to be effective in anti-lung cancer therapy, but its molecular mechanism of action has not been clearly understood.
In this study, we aimed to elucidate the possible molecular mechanism underlying the effect of RR against non-small cell lung cancer (NSCLC) by systems pharmacology.
The effects of RR on NSCLC were examined in Lewis lung carcinoma (LLC) tumor-bearing mice models. The possible molecular mechanism was unraveled by systems pharmacology, which includes pharmacokinetics evaluation, active compounds screening, target prediction and network analysis. Cell proliferation was examined by cell counting kit-8 (CCK-8) assay; cell apoptosis was detected by flow cytometry; protein and proinflammatory cytokines expression were evaluated by Western blot and qRT-PCR.
In vivo, RR significantly inhibited the tumor growth and prolonged the survival of the tumor bearing mice. In silico, we identified 19 potential active molecules (e.g., salidroside and rhodiosin), 112 targets (e.g., COX-2 and AKT) and 27 pathways (e.g., PI3K/AKT signaling pathway and NF-κB signaling pathway) for RR. Additionally, targets analysis and networks construction further revealed that RR exerted anti-cancer effects by regulating apoptosis, angiogenesis and inflammation. In vitro, salidroside could significantly decrease expression of pro-angiogenic factors (e.g., VEGF and eNOS) and proinflammatory cytokines (e.g., COX-2, iNOS and TNF-α). Also, Bcl-2, an anti-apoptotic protein was decreased whereas Bax, a pro-apoptotic protein, was increased. Further flow cytometry analysis showed that salidroside could induce apoptosis in H1975 cells.
Mechanistically, the antitumor effect of RR on NSCLC was responsible for the synergy among anti-inflammatory, anti-angiogenic and pro-apoptotic.
肺癌是全球最常见和致命的癌症。红景天（RR）是一种著名的中药，已被证明在肺癌治疗中有效，但它的作用机制尚不清楚。
本研究旨在通过系统药理学阐明 RR 对非小细胞肺癌（NSCLC）作用的可能分子机制。
在 Lewis 肺癌（LLC）荷瘤小鼠模型中检测 RR 对 NSCLC 的作用。通过系统药理学（包括药代动力学评价、活性化合物筛选、靶点预测和网络分析）揭示可能的分子机制。细胞增殖通过细胞计数试剂盒-8（CCK-8）检测；细胞凋亡通过流式细胞术检测；蛋白质和促炎细胞因子的表达通过 Western blot 和 qRT-PCR 进行评估。
体内，RR 显著抑制肿瘤生长并延长荷瘤小鼠的生存时间。在计算机模拟中，我们鉴定了 19 种潜在的活性化合物（如：红景天苷和红景天素）、112 个靶点（如：COX-2 和 AKT）和 27 条通路（如：PI3K/AKT 信号通路和 NF-κB 信号通路）与 RR 相关。此外，靶点分析和网络构建进一步表明，RR 通过调节凋亡、血管生成和炎症发挥抗癌作用。体外，红景天苷可显著降低促血管生成因子（如：VEGF 和 eNOS）和促炎细胞因子（如：COX-2、iNOS 和 TNF-α）的表达。同时，抗凋亡蛋白 Bcl-2 减少，促凋亡蛋白 Bax 增加。进一步的流式细胞术分析表明，红景天苷可诱导 H1975 细胞凋亡。
从机制上讲，RR 对 NSCLC 的抗肿瘤作用是抗炎、抗血管生成和促凋亡协同作用的结果。
