Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cells

Extensive peritoneal metastasis and malignant ascites continue to pose substantial challenges in achieving favorable treatment outcomes for ovarian cancer. Berberine (BBR), an active component of numerous traditional Chinese herbs, has demonstrated potent anti - tumor effects across various malignan...

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Main Authors: Xiaojie Zhang, Bing Xiong, Yujie Cheng, Jimei Huang, Jiaying Xue, Xiao Li, Wei Lu, Jihui Zhu, Lian Wang, Weihong Yang, Zhongping Cheng
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523325001111
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author Xiaojie Zhang
Bing Xiong
Yujie Cheng
Jimei Huang
Jiaying Xue
Xiao Li
Wei Lu
Jihui Zhu
Lian Wang
Weihong Yang
Zhongping Cheng
author_facet Xiaojie Zhang
Bing Xiong
Yujie Cheng
Jimei Huang
Jiaying Xue
Xiao Li
Wei Lu
Jihui Zhu
Lian Wang
Weihong Yang
Zhongping Cheng
author_sort Xiaojie Zhang
collection DOAJ
description Extensive peritoneal metastasis and malignant ascites continue to pose substantial challenges in achieving favorable treatment outcomes for ovarian cancer. Berberine (BBR), an active component of numerous traditional Chinese herbs, has demonstrated potent anti - tumor effects across various malignancies, including ovarian cancer. In this study, we comprehensively evaluated the impact of BBR on the growth and metastasis of ovarian cancer both in vitro and in vivo. RNA - sequencing was employed to elucidate the underlying mechanisms. Specifically, we investigated lipid metabolism and mitochondrial function in ovarian cancer cells and mice, comparing BBR - treated and untreated groups. Additionally, CIBERSORT analysis and immunohistochemical (IHC) staining were utilized to confirm BBR's ability to enhance the infiltration of tumor-infiltrating immune cells into adipose tissue and improve the inflammatory tumor microenvironment. Our findings indicate that BBR significantly inhibits the growth and metastasis of ovarian cancer in vitro and in vivo. The effects can be attributed to two key processes. Firstly, BBR suppresses the lipid metabolism by downregulating lipid uptake related receptor CD36, lipid metabolic enzyme and mitochondrial function. Secondly, BBR alleviates the aging of adipose tissue and adipose derived stem cells (ADSCs), thereby decreasing the secretion of senescence-associated secretory phenotype (SASP). These ultimately lead to the increasing the improvement of tumor infiltrating immune cells, such as CD4⁺ helper T cells (CD3⁺CD4⁺) and cytotoxic T lymphocytes (CD3⁺CD8⁺), and inflammation in ovarian cancer tissue. Collectively, these findings suggested a potential therapeutic effect of BBR in the treatment of advanced ovarian cancer, particularly cases complicated by peritoneal metastasis and malignant ascites.
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spelling doaj-art-a58c1f4655114faeb554f7b647466c712025-08-20T02:14:38ZengElsevierTranslational Oncology1936-52332025-06-015610238010.1016/j.tranon.2025.102380Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cellsXiaojie Zhang0Bing Xiong1Yujie Cheng2Jimei Huang3Jiaying Xue4Xiao Li5Wei Lu6Jihui Zhu7Lian Wang8Weihong Yang9Zhongping Cheng10Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Department of Gynecology, Jing'an District Hospital of Traditional Chinese Medicine, Shanghai, 200072, PR China; Continuous Education College, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, PR ChinaDepartment of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR ChinaDepartment of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR ChinaContinuous Education College, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, PR ChinaDepartment of Gynecology, Jing'an District Hospital of Traditional Chinese Medicine, Shanghai, 200072, PR China; Continuous Education College, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, PR ChinaDepartment of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR ChinaDepartment of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR ChinaDepartment of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR ChinaDepartment of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Corresponding authors at: Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China.Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Corresponding authors at: Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China.Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China; Corresponding authors at: Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China.Extensive peritoneal metastasis and malignant ascites continue to pose substantial challenges in achieving favorable treatment outcomes for ovarian cancer. Berberine (BBR), an active component of numerous traditional Chinese herbs, has demonstrated potent anti - tumor effects across various malignancies, including ovarian cancer. In this study, we comprehensively evaluated the impact of BBR on the growth and metastasis of ovarian cancer both in vitro and in vivo. RNA - sequencing was employed to elucidate the underlying mechanisms. Specifically, we investigated lipid metabolism and mitochondrial function in ovarian cancer cells and mice, comparing BBR - treated and untreated groups. Additionally, CIBERSORT analysis and immunohistochemical (IHC) staining were utilized to confirm BBR's ability to enhance the infiltration of tumor-infiltrating immune cells into adipose tissue and improve the inflammatory tumor microenvironment. Our findings indicate that BBR significantly inhibits the growth and metastasis of ovarian cancer in vitro and in vivo. The effects can be attributed to two key processes. Firstly, BBR suppresses the lipid metabolism by downregulating lipid uptake related receptor CD36, lipid metabolic enzyme and mitochondrial function. Secondly, BBR alleviates the aging of adipose tissue and adipose derived stem cells (ADSCs), thereby decreasing the secretion of senescence-associated secretory phenotype (SASP). These ultimately lead to the increasing the improvement of tumor infiltrating immune cells, such as CD4⁺ helper T cells (CD3⁺CD4⁺) and cytotoxic T lymphocytes (CD3⁺CD8⁺), and inflammation in ovarian cancer tissue. Collectively, these findings suggested a potential therapeutic effect of BBR in the treatment of advanced ovarian cancer, particularly cases complicated by peritoneal metastasis and malignant ascites.http://www.sciencedirect.com/science/article/pii/S1936523325001111BerberineOvarian cancerTumor infiltrating immune cellsPeritoneal metastasisMalignant ascites
spellingShingle Xiaojie Zhang
Bing Xiong
Yujie Cheng
Jimei Huang
Jiaying Xue
Xiao Li
Wei Lu
Jihui Zhu
Lian Wang
Weihong Yang
Zhongping Cheng
Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cells
Translational Oncology
Berberine
Ovarian cancer
Tumor infiltrating immune cells
Peritoneal metastasis
Malignant ascites
title Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cells
title_full Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cells
title_fullStr Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cells
title_full_unstemmed Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cells
title_short Berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism, alleviating aging of adipose tissue and increasing tumor infiltrating immune cells
title_sort berberine inhibits metastasis of ovarian cancer by blocking lipid metabolism alleviating aging of adipose tissue and increasing tumor infiltrating immune cells
topic Berberine
Ovarian cancer
Tumor infiltrating immune cells
Peritoneal metastasis
Malignant ascites
url http://www.sciencedirect.com/science/article/pii/S1936523325001111
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