Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology Study
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...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/6/758 |
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| author | Xiaodan Xue Yannan Liu Linlin Qu Cuiying Fan Xiaoxuan Ma Pingkai Ouyang Daidi Fan |
| author_facet | Xiaodan Xue Yannan Liu Linlin Qu Cuiying Fan Xiaoxuan Ma Pingkai Ouyang Daidi Fan |
| author_sort | Xiaodan Xue |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T22:46:49Z |
| format | Article |
| id | doaj.art-c54b9d4d339b4d7eab34172a12edeae8 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:46:49Z |
| publishDate | 2022-06-01 |
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| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-c54b9d4d339b4d7eab34172a12edeae82023-11-23T18:28:13ZengMDPI AGPharmaceuticals1424-82472022-06-0115675810.3390/ph15060758Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology StudyXiaodan Xue0Yannan Liu1Linlin Qu2Cuiying Fan3Xiaoxuan Ma4Pingkai Ouyang5Daidi Fan6Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi’an 710069, ChinaShaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi’an 710069, ChinaShaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi’an 710069, ChinaXi’an Giant Biotechnology Co., Ltd., Xi’an 710076, ChinaShaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi’an 710069, ChinaCollege of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, ChinaShaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi’an 710069, ChinaLung 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.https://www.mdpi.com/1424-8247/15/6/758ginsenoside Rh3network pharmacologyhuman lung cancermetastasisERK |
| spellingShingle | Xiaodan Xue Yannan Liu Linlin Qu Cuiying Fan Xiaoxuan Ma Pingkai Ouyang Daidi Fan Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology Study Pharmaceuticals ginsenoside Rh3 network pharmacology human lung cancer metastasis ERK |
| title | Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology Study |
| title_full | Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology Study |
| title_fullStr | Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology Study |
| title_full_unstemmed | Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology Study |
| title_short | Ginsenoside Rh3 Inhibits Lung Cancer Metastasis by Targeting Extracellular Signal-Regulated Kinase: A Network Pharmacology Study |
| title_sort | ginsenoside rh3 inhibits lung cancer metastasis by targeting extracellular signal regulated kinase a network pharmacology study |
| topic | ginsenoside Rh3 network pharmacology human lung cancer metastasis ERK |
| url | https://www.mdpi.com/1424-8247/15/6/758 |
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