Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, Lubbock, Texas 79416, United States; Department of Respiratory Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, China.
Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, Lubbock, Texas 79416, United States.
J Ethnopharmacol. 2018 May 10;217:140-151. doi: 10.1016/j.jep.2018.02.020. Epub 2018 Feb 16.
Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells.
Four different NSCLC cell lines (A549, H460, H1650, and H1975) were used. Cytotoxicity, in vitro tumorigenicity, gene expression, and protein expression were analyzed by MTT assay, soft agar assay, real-time PCR, and Western blots, respectively.
Among the 14 components in LJSJF, SB was the only one to possess cytotoxic effects at its pharmacologically relevant doses. Additionally, we observed synergistically dose-dependent cytotoxic effects of SB in combination with other LJSJF components. After SB or LJSJF treatment, significant reductions in colony number and/or size were observed in A549 and H460; a notable dose-dependent decrease in EGFR was observed in A549, H460, and H1650; significant downregulation in EGFR and its downstream signaling targets mTOR and p38MAPK were also observed in A549 and H460; and p53 and p21 were significantly increased while survivin, cyclin D1, and MDM2 were significantly decreased in A549. Additionally, p53, p21, and Mettl7b were decreased, but p73 was increased in H460. Neither EGFR nor p53 was changed in H1975. Therefore, SB or LJSJF may induce cytotoxic effects by regulating multiple and/or distinct apoptotic pathways in different NSCLC cells.
LJSJF exerts more pronounced cytotoxic effects against NSCLC cells than SB does by synergistically regulating the underlining molecular mechanisms including EGFR and/or p53 signaling pathways.
经验性草药医学作为现代西方医学的补充，引发了一系列研究，以寻找新型抗癌药物。黄芩（SB）常用于治疗不同类型的癌症，但它的作用机制尚不清楚。在这项研究中，我们试图阐明一种由 14 种成分组成的中药方剂的作用模式，名为连加散结方（LJSJF），其中 SB 是针对非小细胞肺癌（NSCLC）细胞的“原则”。
使用四种不同的 NSCLC 细胞系（A549、H460、H1650 和 H1975）。通过 MTT 测定、软琼脂测定、实时 PCR 和 Western blot 分别分析细胞毒性、体外致瘤性、基因表达和蛋白表达。
在 LJSJF 的 14 种成分中，SB 是唯一一种在其药理学相关剂量下具有细胞毒性作用的成分。此外，我们观察到 SB 与其他 LJSJF 成分联合使用时具有协同剂量依赖性的细胞毒性作用。在 SB 或 LJSJF 处理后，A549 和 H460 的菌落数量和/或大小明显减少；A549、H460 和 H1650 中 EGFR 的表达明显下降；A549 和 H460 中 EGFR 及其下游信号靶标 mTOR 和 p38MAPK 的表达也明显下调；A549 中 p53 和 p21 明显增加，而 survivin、cyclin D1 和 MDM2 明显减少。此外，H460 中 p53、p21 和 Mettl7b 减少，p73 增加。H1975 中 EGFR 或 p53 未发生变化。因此，SB 或 LJSJF 可能通过调节多种和/或不同的凋亡途径在不同的 NSCLC 细胞中诱导细胞毒性作用。
LJSJF 通过协同调节包括 EGFR 和/或 p53 信号通路在内的潜在分子机制，对 NSCLC 细胞产生比 SB 更明显的细胞毒性作用。
