Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway
Yanshi Wang, Shaojie Yang, Shanshan Zhang, Xin Wu Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People’s Republic of ChinaCorrespondence: Xin WuThe First Affiliated Hospital of China Medical University, 155 Nanjing North Roa...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2020-03-01
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| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/oxymatrine-inhibits-proliferation-and-migration-of-vulvar-squamous-cel-peer-reviewed-article-CMAR |
| _version_ | 1818389231727280128 |
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| author | Wang Y Yang S Zhang S Wu X |
| author_facet | Wang Y Yang S Zhang S Wu X |
| author_sort | Wang Y |
| collection | DOAJ |
| description | Yanshi Wang, Shaojie Yang, Shanshan Zhang, Xin Wu Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People’s Republic of ChinaCorrespondence: Xin WuThe First Affiliated Hospital of China Medical University, 155 Nanjing North Road, Shenyang, Liaoning 110000, People’s Republic of ChinaTel +86-13940408181Fax +8624-83696110Email wuxin@cmu.edu.cnPurpose: To evaluate the anti-tumor effects of oxymatrine in vulvar squamous cell carcinoma (VSCC) cells and to explore the underlying mechanisms.Methods: We selected SW962 and A431 VSCC cell lines. Cell proliferation was examined using MTT assay. Cell cycle and apoptosis were detected using flow cytometry. Migration and invasion were evaluated using transwell and wound-healing assays. The relevant protein expression and signaling pathways were analyzed using Western blotting.Results: Oxymatrine inhibited the proliferation of SW962 and A431 VSCC cells in a time- and dose-dependent manner. Oxymatrine induced cell cycle arrest in the G2/M phase by increasing the protein expression of P21 and decreasing levels of cyclin B1 and CDC2. Oxymatrine upregulated the expression of cleaved-caspase 3 and BAX and downregulated the expression of BCL2, which led to an increase in apoptosis. Oxymatrine also suppressed the migration and invasion of SW962 and A431 cells by reducing levels of MMP2 and MMP9. After treatment with oxymatrine or a RAS inhibitor (salirasib), expression levels of RAS, p-RAF, p-MEK, p-ERK, C-MYC, and MMP2 were reduced. When TGF-β 1 was used to stimulate SW962 and A431 cells, the expression of the above proteins increased; this increase was reversed by using oxymatrine or salirasib again.Conclusion: Oxymatrine inhibits proliferation and migration of VSCC cells by blocking the RAS/RAF/MEK/ERK pathway.Keywords: oxymatrine, vulvar squamous cell carcinoma, RAS/RAF/MEK/ERK |
| first_indexed | 2024-12-14T04:38:27Z |
| format | Article |
| id | doaj.art-68d8cf8432e544aaa30545fd835235bb |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-14T04:38:27Z |
| publishDate | 2020-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-68d8cf8432e544aaa30545fd835235bb2022-12-21T23:16:51ZengDove Medical PressCancer Management and Research1179-13222020-03-01Volume 122057206752605Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK PathwayWang YYang SZhang SWu XYanshi Wang, Shaojie Yang, Shanshan Zhang, Xin Wu Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People’s Republic of ChinaCorrespondence: Xin WuThe First Affiliated Hospital of China Medical University, 155 Nanjing North Road, Shenyang, Liaoning 110000, People’s Republic of ChinaTel +86-13940408181Fax +8624-83696110Email wuxin@cmu.edu.cnPurpose: To evaluate the anti-tumor effects of oxymatrine in vulvar squamous cell carcinoma (VSCC) cells and to explore the underlying mechanisms.Methods: We selected SW962 and A431 VSCC cell lines. Cell proliferation was examined using MTT assay. Cell cycle and apoptosis were detected using flow cytometry. Migration and invasion were evaluated using transwell and wound-healing assays. The relevant protein expression and signaling pathways were analyzed using Western blotting.Results: Oxymatrine inhibited the proliferation of SW962 and A431 VSCC cells in a time- and dose-dependent manner. Oxymatrine induced cell cycle arrest in the G2/M phase by increasing the protein expression of P21 and decreasing levels of cyclin B1 and CDC2. Oxymatrine upregulated the expression of cleaved-caspase 3 and BAX and downregulated the expression of BCL2, which led to an increase in apoptosis. Oxymatrine also suppressed the migration and invasion of SW962 and A431 cells by reducing levels of MMP2 and MMP9. After treatment with oxymatrine or a RAS inhibitor (salirasib), expression levels of RAS, p-RAF, p-MEK, p-ERK, C-MYC, and MMP2 were reduced. When TGF-β 1 was used to stimulate SW962 and A431 cells, the expression of the above proteins increased; this increase was reversed by using oxymatrine or salirasib again.Conclusion: Oxymatrine inhibits proliferation and migration of VSCC cells by blocking the RAS/RAF/MEK/ERK pathway.Keywords: oxymatrine, vulvar squamous cell carcinoma, RAS/RAF/MEK/ERKhttps://www.dovepress.com/oxymatrine-inhibits-proliferation-and-migration-of-vulvar-squamous-cel-peer-reviewed-article-CMARoxymatrinevulvar squamous cell carcinomaras/raf/mek/erk |
| spellingShingle | Wang Y Yang S Zhang S Wu X Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway Cancer Management and Research oxymatrine vulvar squamous cell carcinoma ras/raf/mek/erk |
| title | Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway |
| title_full | Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway |
| title_fullStr | Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway |
| title_full_unstemmed | Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway |
| title_short | Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway |
| title_sort | oxymatrine inhibits proliferation and migration of vulvar squamous cell carcinoma cells via attenuation of the ras raf mek erk pathway |
| topic | oxymatrine vulvar squamous cell carcinoma ras/raf/mek/erk |
| url | https://www.dovepress.com/oxymatrine-inhibits-proliferation-and-migration-of-vulvar-squamous-cel-peer-reviewed-article-CMAR |
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