Xue Xiaodan, Liu Yannan, Qu Linlin, Fan Cuiying, Ma Xiaoxuan, Ouyang Pingkai, Fan Daidi
Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an 710069, China.
Shaanxi R & D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an 710069, China.
Pharmaceuticals (Basel). 2022 Jun 17;15(6):758. doi: 10.3390/ph15060758.
Lung cancer has a high mortality rate and is very common. One of the main reasons for the poor prognosis of patients with lung cancer is the high incidence of metastasis. Ginsenoside Rh3, a rare ginsenoside extracted from Panax notoginseng, exhibits excellent anti-inflammatory and anti-tumor effects. Nonetheless, the inhibitory potential of Rh3 against lung cancer remains unknown. The target genes of Rh3 were screened by the PharmMapper database; the proliferation of lung cancer cells was detected by MTT assay; the migration and invasion of cells were detected by the Transwell method; and the expression of extracellular signal-regulated kinase (ERK) and EMT-related proteins in vivo and in vitro were detected by Western blotting. In addition, we established a lung metastasis model in nude mice using A549 cells to assess the effect of Rh3 on NSCLC tumor metastasis in vivo. Our findings suggest that Rh3 significantly inhibited lung cancer metastasis both in vivo and in vitro. It was determined by flow cytometry analysis that Rh3 notably inhibited cell proliferation by blocking the G1 phase. In addition, Rh3 inhibited metastasis in lung cancer cells and regulated the expression of metastasis-related proteins under hypoxia. Mechanistic studies suggested that Rh3 targeted ERK to inhibit lung cancer metastasis. The ERK inhibitor U0126 or siRNA-mediated knockdown of ERK had an enhanced effect on Rh3's ability to inhibit lung cancer metastasis. The studies revealed that the inhibitory effect of Rh3 on the metastatic ability of lung cancer cells may be supported by ERK-related signaling pathways.
肺癌死亡率高且极为常见。肺癌患者预后不佳的主要原因之一是转移发生率高。人参皂苷Rh3是从三七中提取的一种稀有皂苷，具有出色的抗炎和抗肿瘤作用。尽管如此，Rh3对肺癌的抑制潜力仍不清楚。通过PharmMapper数据库筛选Rh3的靶基因；采用MTT法检测肺癌细胞的增殖；用Transwell法检测细胞的迁移和侵袭；通过蛋白质免疫印迹法检测细胞外信号调节激酶（ERK）和EMT相关蛋白在体内和体外的表达。此外，我们用A549细胞在裸鼠中建立了肺转移模型，以评估Rh3对非小细胞肺癌肿瘤转移的体内作用。我们的研究结果表明，Rh3在体内和体外均能显著抑制肺癌转移。通过流式细胞术分析确定，Rh3通过阻断G1期显著抑制细胞增殖。此外，Rh3在缺氧条件下抑制肺癌细胞的转移并调节转移相关蛋白的表达。机制研究表明，Rh3靶向ERK以抑制肺癌转移。ERK抑制剂U0126或siRNA介导的ERK敲低对Rh3抑制肺癌转移的能力有增强作用。这些研究表明，Rh3对肺癌细胞转移能力的抑制作用可能由ERK相关信号通路支持。
