Rui Feng, Zhongxing Li, Yuejun Jia, Yali Ji, Meitian Guo, Xing Wang
{"title":"白花蛇耳草总黄酮通过PIAS4/STAT3通路促进AR泛素化和降解抑制前列腺癌进展","authors":"Rui Feng, Zhongxing Li, Yuejun Jia, Yali Ji, Meitian Guo, Xing Wang","doi":"10.1002/cbin.70070","DOIUrl":null,"url":null,"abstract":"<p><p>Total flavonoids of Hedyotis diffusa Willd (TFHDW) is an active compound extracted from Hedyotis diffusa Willd (HDW), one of the most well-known herbs possessing antitumor effects. In this study, the potential antitumor effects of TFHDW were investigated in vitro in mouse prostate cancer cells RM1 and human prostate cancer cells LNCaP and in vivo using a xenograft tumor model involving injection of RM1 cells. Upon TFHDW treatment, RM1 and LNCaP cells exhibited augmented protein expression of the protein inhibitor of activated STAT (PIAS4) and diminished activity of signal transducer and activator of transcription 3 (STAT3), along with impaired proliferative, migratory, and invasive capacities. Ectopic STAT3 expression or PIAS4 silencing in RM1 and LNCaP cells partly annulled the inhibition effect of TFHDW treatment on cell malignant phenotypes. Mechanistic studies revealed that TFHDW elevated transcriptional activity of damage-specific DNA-binding protein 2 via PIAS4/STAT3, consequently enhancing ubiquitination and degradation of androgen receptor (AR) protein. By this, TFHDW alleviated the growth of prostate cancer in vitro and in vivo. Altogether, our work uncovers new insights into the link between TFHDW and the PIAS4/STAT3/AR axis in prostate cancer. These findings may provide a novel therapeutic option for targeting the PIAS4/STAT3/AR axis in prostate cancer.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Total Flavonoids of Hedyotis Diffusa Willd Suppresses Prostate Cancer Progression by Promoting AR Ubiquitination and Degradation via the PIAS4/STAT3 Pathway.\",\"authors\":\"Rui Feng, Zhongxing Li, Yuejun Jia, Yali Ji, Meitian Guo, Xing Wang\",\"doi\":\"10.1002/cbin.70070\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Total flavonoids of Hedyotis diffusa Willd (TFHDW) is an active compound extracted from Hedyotis diffusa Willd (HDW), one of the most well-known herbs possessing antitumor effects. In this study, the potential antitumor effects of TFHDW were investigated in vitro in mouse prostate cancer cells RM1 and human prostate cancer cells LNCaP and in vivo using a xenograft tumor model involving injection of RM1 cells. Upon TFHDW treatment, RM1 and LNCaP cells exhibited augmented protein expression of the protein inhibitor of activated STAT (PIAS4) and diminished activity of signal transducer and activator of transcription 3 (STAT3), along with impaired proliferative, migratory, and invasive capacities. Ectopic STAT3 expression or PIAS4 silencing in RM1 and LNCaP cells partly annulled the inhibition effect of TFHDW treatment on cell malignant phenotypes. Mechanistic studies revealed that TFHDW elevated transcriptional activity of damage-specific DNA-binding protein 2 via PIAS4/STAT3, consequently enhancing ubiquitination and degradation of androgen receptor (AR) protein. By this, TFHDW alleviated the growth of prostate cancer in vitro and in vivo. Altogether, our work uncovers new insights into the link between TFHDW and the PIAS4/STAT3/AR axis in prostate cancer. These findings may provide a novel therapeutic option for targeting the PIAS4/STAT3/AR axis in prostate cancer.</p>\",\"PeriodicalId\":9806,\"journal\":{\"name\":\"Cell Biology International\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-08-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Biology International\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/cbin.70070\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology International","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/cbin.70070","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Total Flavonoids of Hedyotis Diffusa Willd Suppresses Prostate Cancer Progression by Promoting AR Ubiquitination and Degradation via the PIAS4/STAT3 Pathway.
Total flavonoids of Hedyotis diffusa Willd (TFHDW) is an active compound extracted from Hedyotis diffusa Willd (HDW), one of the most well-known herbs possessing antitumor effects. In this study, the potential antitumor effects of TFHDW were investigated in vitro in mouse prostate cancer cells RM1 and human prostate cancer cells LNCaP and in vivo using a xenograft tumor model involving injection of RM1 cells. Upon TFHDW treatment, RM1 and LNCaP cells exhibited augmented protein expression of the protein inhibitor of activated STAT (PIAS4) and diminished activity of signal transducer and activator of transcription 3 (STAT3), along with impaired proliferative, migratory, and invasive capacities. Ectopic STAT3 expression or PIAS4 silencing in RM1 and LNCaP cells partly annulled the inhibition effect of TFHDW treatment on cell malignant phenotypes. Mechanistic studies revealed that TFHDW elevated transcriptional activity of damage-specific DNA-binding protein 2 via PIAS4/STAT3, consequently enhancing ubiquitination and degradation of androgen receptor (AR) protein. By this, TFHDW alleviated the growth of prostate cancer in vitro and in vivo. Altogether, our work uncovers new insights into the link between TFHDW and the PIAS4/STAT3/AR axis in prostate cancer. These findings may provide a novel therapeutic option for targeting the PIAS4/STAT3/AR axis in prostate cancer.
期刊介绍:
Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect.
These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.