Study on the mechanism by which Xuanfu Hua Tang increases sensitivity of hepatocellular carcinoma cells to sorafenib by antagonizing the Notch1 pathway through HIF-2α
BackgroundIt is crucial to explore ways to increase the sensitivity of hepatocellular carcinoma cells to sorafenib.MethodsThe HepG2 and Huh7 cell lines with overexpressed HIF-2α were constructed. The cells were treated with Xuanfu Hua Tang (Xuanfu HT) containing serum and sorafenib separately and by...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1552480/full |
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| author | Wenzhao Luo Wenzhao Luo Xian Li Yiwan Shang Yiwan Shang Zhen Chen Yinglin Cui |
| author_facet | Wenzhao Luo Wenzhao Luo Xian Li Yiwan Shang Yiwan Shang Zhen Chen Yinglin Cui |
| author_sort | Wenzhao Luo |
| collection | DOAJ |
| description | BackgroundIt is crucial to explore ways to increase the sensitivity of hepatocellular carcinoma cells to sorafenib.MethodsThe HepG2 and Huh7 cell lines with overexpressed HIF-2α were constructed. The cells were treated with Xuanfu Hua Tang (Xuanfu HT) containing serum and sorafenib separately and by using both of them, the cell viability and other cell biology functions were detected by CCK-8 and other assays. The mechanism of quercetin was investigated by thermal stability assay and dual luciferase reporter gene assay, and the effects of Xuanfu HT on the transcript and protein levels of Notch1 pathway genes were evaluated by qPCR and Western Blot. The effects of Xuanfu HT in tumor growth was investigates by mice subcutaneous tumor implantation model.ResultsThe Xuanfu HT increased sensitivity of HepG2 and Huh7 cell lines with overexpressed HIF-2αto sorafenib, and enhanced inhibition of cell proliferation, migration, invasion and angiogenesis by sorafenib. The component quercetin of Xuanfu HT containing serum could inhibit the binding between HIF-2α and the promoter of the transcription factor FOXP3 to inhibit the expression of FOXP3, so as to inhibit the activation of Notch1 pathway and angiogenesis. The expression of FOXP3 counteracted the decrease in Notch1 and VEGF expression, and angiogenic capacity induced by the combined treatment with Xuanfu HT and sorafenib. The tumor growth inhibitory effects of Xuanfu HT and sorafenib in mice were proved by constructing a subcutaneous tumor model.ConclusionXuanfu HT can increase sorafenib sensitivity of hepatocellular carcinoma cells by antagonizing the Notch1 pathway through quercetin-binding HIF-2α. |
| format | Article |
| id | doaj-art-6568c853ea3940d8a98ee6b9a4d89ce5 |
| institution | OA Journals |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-6568c853ea3940d8a98ee6b9a4d89ce52025-08-20T02:30:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-05-011510.3389/fonc.2025.15524801552480Study on the mechanism by which Xuanfu Hua Tang increases sensitivity of hepatocellular carcinoma cells to sorafenib by antagonizing the Notch1 pathway through HIF-2αWenzhao Luo0Wenzhao Luo1Xian Li2Yiwan Shang3Yiwan Shang4Zhen Chen5Yinglin Cui6Henan University of Chinese Medicine, School of Basic Medicine (Zhongjing School), Zhengzhou, Henan, ChinaHenan Province Hospital of Traditional Chinese Medicine, Department of Hepatobiliary and Spleen Stomach, Zhengzhou, Henan, ChinaHenan Province Hospital of Traditional Chinese Medicine, Department of Hepatobiliary and Spleen Stomach, Zhengzhou, Henan, ChinaHenan University of Chinese Medicine, School of Basic Medicine (Zhongjing School), Zhengzhou, Henan, ChinaHenan University of Chinese Medicine, Academy of Chinese Medical Sciences, Zhengzhou, Henan, ChinaHenan University of Chinese Medicine, Academy of Chinese Medical Sciences, Zhengzhou, Henan, ChinaHenan Province Hospital of Traditional Chinese Medicine, Department of Hepatobiliary and Spleen Stomach, Zhengzhou, Henan, ChinaBackgroundIt is crucial to explore ways to increase the sensitivity of hepatocellular carcinoma cells to sorafenib.MethodsThe HepG2 and Huh7 cell lines with overexpressed HIF-2α were constructed. The cells were treated with Xuanfu Hua Tang (Xuanfu HT) containing serum and sorafenib separately and by using both of them, the cell viability and other cell biology functions were detected by CCK-8 and other assays. The mechanism of quercetin was investigated by thermal stability assay and dual luciferase reporter gene assay, and the effects of Xuanfu HT on the transcript and protein levels of Notch1 pathway genes were evaluated by qPCR and Western Blot. The effects of Xuanfu HT in tumor growth was investigates by mice subcutaneous tumor implantation model.ResultsThe Xuanfu HT increased sensitivity of HepG2 and Huh7 cell lines with overexpressed HIF-2αto sorafenib, and enhanced inhibition of cell proliferation, migration, invasion and angiogenesis by sorafenib. The component quercetin of Xuanfu HT containing serum could inhibit the binding between HIF-2α and the promoter of the transcription factor FOXP3 to inhibit the expression of FOXP3, so as to inhibit the activation of Notch1 pathway and angiogenesis. The expression of FOXP3 counteracted the decrease in Notch1 and VEGF expression, and angiogenic capacity induced by the combined treatment with Xuanfu HT and sorafenib. The tumor growth inhibitory effects of Xuanfu HT and sorafenib in mice were proved by constructing a subcutaneous tumor model.ConclusionXuanfu HT can increase sorafenib sensitivity of hepatocellular carcinoma cells by antagonizing the Notch1 pathway through quercetin-binding HIF-2α.https://www.frontiersin.org/articles/10.3389/fonc.2025.1552480/fullXuanfu Huahepatocellular carcinomasorafenibNOTCH1FOXP3 |
| spellingShingle | Wenzhao Luo Wenzhao Luo Xian Li Yiwan Shang Yiwan Shang Zhen Chen Yinglin Cui Study on the mechanism by which Xuanfu Hua Tang increases sensitivity of hepatocellular carcinoma cells to sorafenib by antagonizing the Notch1 pathway through HIF-2α Frontiers in Oncology Xuanfu Hua hepatocellular carcinoma sorafenib NOTCH1 FOXP3 |
| title | Study on the mechanism by which Xuanfu Hua Tang increases sensitivity of hepatocellular carcinoma cells to sorafenib by antagonizing the Notch1 pathway through HIF-2α |
| title_full | Study on the mechanism by which Xuanfu Hua Tang increases sensitivity of hepatocellular carcinoma cells to sorafenib by antagonizing the Notch1 pathway through HIF-2α |
| title_fullStr | Study on the mechanism by which Xuanfu Hua Tang increases sensitivity of hepatocellular carcinoma cells to sorafenib by antagonizing the Notch1 pathway through HIF-2α |
| title_full_unstemmed | Study on the mechanism by which Xuanfu Hua Tang increases sensitivity of hepatocellular carcinoma cells to sorafenib by antagonizing the Notch1 pathway through HIF-2α |
| title_short | Study on the mechanism by which Xuanfu Hua Tang increases sensitivity of hepatocellular carcinoma cells to sorafenib by antagonizing the Notch1 pathway through HIF-2α |
| title_sort | study on the mechanism by which xuanfu hua tang increases sensitivity of hepatocellular carcinoma cells to sorafenib by antagonizing the notch1 pathway through hif 2α |
| topic | Xuanfu Hua hepatocellular carcinoma sorafenib NOTCH1 FOXP3 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1552480/full |
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