Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis
The incidence of Poorly cohesive carcinoma (PCC) has steadily risen in recent years, posing a significant clinical challenge. To reveal the anti-tumor effects of Jianpi Yangzheng Xiaozheng granule (JPYZXZ) in PCC, an initial investigation was performed using CCK-8, colony formation, scratch, and tra...
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Frontiers Media S.A.
2025-02-01
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| author | Xiangyang Wang Xiangyang Wang Jingxiao Li Jingxiao Li Rong Qin Rong Qin Yi Yin Yi Yin Jiepin Li Jiepin Li Sitian Lin Sitian Lin Xi Zou Xi Zou |
| author_facet | Xiangyang Wang Xiangyang Wang Jingxiao Li Jingxiao Li Rong Qin Rong Qin Yi Yin Yi Yin Jiepin Li Jiepin Li Sitian Lin Sitian Lin Xi Zou Xi Zou |
| author_sort | Xiangyang Wang |
| collection | DOAJ |
| description | The incidence of Poorly cohesive carcinoma (PCC) has steadily risen in recent years, posing a significant clinical challenge. To reveal the anti-tumor effects of Jianpi Yangzheng Xiaozheng granule (JPYZXZ) in PCC, an initial investigation was performed using CCK-8, colony formation, scratch, and transwell assays. This was followed by network pharmacology studies to gain a deeper understanding of JPYZXZ’s impact on gastric cancer (GC). Then reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), glutathione (GSH), Oil Red O staining, BODIPY493/503, triglyceride (TG), and cholesterol (TC) assay kits and western blot (Wb) analysis were applied to exam the regulatory effects of JPYZXZ on ferroptosis and lipid metabolism. Additionally, molecular docking studies and Wb analysis were used to further investigate the mechanisms of JPYZXZ on PCC. Finally, in vivo animal studies were conducted. The results show that JPYZXZ can inhibit the proliferation and migration of PCC cell. It increases the levels of ROS, Fe2+, MDA, while declining the content of GSH, TC, TG, and lipid droplet accumulation within cellular compartments. Wb indicates that JPYZXZ can negatively regulate the expression of proteins, including glutathione peroxidase 4 (GPX4), cystine/glutamate antipoter SLC7A11 (xCT), fatty acid synthase (FASN), and acetyl coenzyme A carboxylase 1 (ACC1). Furthermore, ferrostatin-1 (fer-1) is able to reverse the effects of JPYZXZ on the aforementioned markers of ferroptosis and lipid metabolism. Molecular docking analyses reveal that JPYZXZ exhibits a favorable binding affinity towards Stearoyl-Coenzyme A desaturase 1 (SCD1). Mechanism studies demonstrate that JPYZXZ is capable of down-regulating the expressions of proteins like SCD1, β-catenin, GPX4, and xCT, which is analogous to the effects of SCD1 knockdown and the application of SCD1 inhibitor A939572. Nevertheless, when SCD1 is knocked down, JPYZXZ is unable to further downregulate the expressions of these proteins. Animal studies have corroborated the in vitro tumor-inhibiting effects of JPYZXZ. Therefore, this study offers the first evidence that JPYZXZ inhibits PCC progression by orchestrating ferroptosis and altering lipid metabolism, mediated by the SCD1/Wnt/β-catenin pathway. |
| format | Article |
| id | doaj-art-c3998181ddf44ac6a8d526b0cfa98bc1 |
| institution | DOAJ |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-c3998181ddf44ac6a8d526b0cfa98bc12025-08-20T03:11:06ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-02-011210.3389/fmolb.2025.15234941523494Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axisXiangyang Wang0Xiangyang Wang1Jingxiao Li2Jingxiao Li3Rong Qin4Rong Qin5Yi Yin6Yi Yin7Jiepin Li8Jiepin Li9Sitian Lin10Sitian Lin11Xi Zou12Xi Zou13Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, ChinaNo. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, ChinaNo. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Medical Oncology, Jiangsu University Affiliated People’s Hospital, Zhenjiang, Jiangsu, ChinaZhenjiang Clinical Medical College of Nanjing Medical University, Zhenjiang, Jiangsu, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, ChinaNo. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, ChinaNo. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, ChinaNo. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, ChinaNo. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaThe incidence of Poorly cohesive carcinoma (PCC) has steadily risen in recent years, posing a significant clinical challenge. To reveal the anti-tumor effects of Jianpi Yangzheng Xiaozheng granule (JPYZXZ) in PCC, an initial investigation was performed using CCK-8, colony formation, scratch, and transwell assays. This was followed by network pharmacology studies to gain a deeper understanding of JPYZXZ’s impact on gastric cancer (GC). Then reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), glutathione (GSH), Oil Red O staining, BODIPY493/503, triglyceride (TG), and cholesterol (TC) assay kits and western blot (Wb) analysis were applied to exam the regulatory effects of JPYZXZ on ferroptosis and lipid metabolism. Additionally, molecular docking studies and Wb analysis were used to further investigate the mechanisms of JPYZXZ on PCC. Finally, in vivo animal studies were conducted. The results show that JPYZXZ can inhibit the proliferation and migration of PCC cell. It increases the levels of ROS, Fe2+, MDA, while declining the content of GSH, TC, TG, and lipid droplet accumulation within cellular compartments. Wb indicates that JPYZXZ can negatively regulate the expression of proteins, including glutathione peroxidase 4 (GPX4), cystine/glutamate antipoter SLC7A11 (xCT), fatty acid synthase (FASN), and acetyl coenzyme A carboxylase 1 (ACC1). Furthermore, ferrostatin-1 (fer-1) is able to reverse the effects of JPYZXZ on the aforementioned markers of ferroptosis and lipid metabolism. Molecular docking analyses reveal that JPYZXZ exhibits a favorable binding affinity towards Stearoyl-Coenzyme A desaturase 1 (SCD1). Mechanism studies demonstrate that JPYZXZ is capable of down-regulating the expressions of proteins like SCD1, β-catenin, GPX4, and xCT, which is analogous to the effects of SCD1 knockdown and the application of SCD1 inhibitor A939572. Nevertheless, when SCD1 is knocked down, JPYZXZ is unable to further downregulate the expressions of these proteins. Animal studies have corroborated the in vitro tumor-inhibiting effects of JPYZXZ. Therefore, this study offers the first evidence that JPYZXZ inhibits PCC progression by orchestrating ferroptosis and altering lipid metabolism, mediated by the SCD1/Wnt/β-catenin pathway.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1523494/fulltraditional Chinese medicinepoorly cohesive carcinomaferroptosislipid metabolismnetwork pharmacology |
| spellingShingle | Xiangyang Wang Xiangyang Wang Jingxiao Li Jingxiao Li Rong Qin Rong Qin Yi Yin Yi Yin Jiepin Li Jiepin Li Sitian Lin Sitian Lin Xi Zou Xi Zou Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis Frontiers in Molecular Biosciences traditional Chinese medicine poorly cohesive carcinoma ferroptosis lipid metabolism network pharmacology |
| title | Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis |
| title_full | Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis |
| title_fullStr | Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis |
| title_full_unstemmed | Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis |
| title_short | Jianpi Yangzheng Xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via SCD1/Wnt/β-catenin axis |
| title_sort | jianpi yangzheng xiaozheng granule induced ferroptosis to suppress gastric cancer progression through reprogramming lipid metabolism via scd1 wnt β catenin axis |
| topic | traditional Chinese medicine poorly cohesive carcinoma ferroptosis lipid metabolism network pharmacology |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1523494/full |
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