Radix Bupleuri-Radix Paeoniae Alba Inhibits the Development of Hepatocellular Carcinoma through Activation of the PTEN/PD-L1 Axis within the Immune Microenvironment

Zhang, Fan1; Zhou, Kun2; Yuan, Wei3; Sun, Kewei3,4

2023-10-01

10.1080/01635581.2023.2276525

NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL   Impact Factor & Quartile

0163-5581

1532-7914

ObjectiveThis study investigated how Radix Bupleuri-Radix Paeoniae Alba (BP) was active against hepatocellular carcinoma (HCC).MethodsTraditional Chinese medicine systems pharmacology (TCMSP) database was employed to determine the active ingredients of BP and potential targets against HCC. Molecular docking analysis verified the binding activity of PTEN with BP ingredients. H22 cells were used to establish an HCC model in male balb/c mice. Immunofluorescence staining, immunohistochemistry, flow cytometry, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative PCR were used to study changes in proliferation, apoptosis, PTEN levels, inflammation, and T-cell differentiation in male balb/c mice.ResultsThe major active ingredients in BP were found to be quercetin, kaempferol, isorhamnetin, stigmasterol, and beta-sitosterol. Molecular docking demonstrated that these five active BP ingredients formed a stable complex with PTEN. BP exhibited an anti-tumor effect in our HCC mouse model. BP was found to increase the CD8+ and IFN-gamma+/CD4+ T cell levels while decreasing the PD-1+/CD8+ T and Treg cell levels in HCC mice. BP up-regulated the IL-6, IFN-gamma, and TNF-alpha levels but down-regulated the IL-10 levels in HCC mice. After PTEN knockdown, BP-induced effects were abrogated.ConclusionBP influenced the immune microenvironment through activation of the PTEN/PD-L1 axis, protecting against HCC.

SCI

English

First

Shenzhen Science and Technology Innovation Fund ([2022])["47","JCYJ20220530163407018"] ; Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Research on Internal Topics[22240G1045]

Oncology ; Nutrition & Dietetics

Oncology ; Nutrition & Dietetics

WOS:001092310900001

ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD

CLINICAL MEDICINE

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Dept TCM, Affiliated Hosp 2, Shenzhen, Guangdong, Peoples R China
2.Guangzhou Univ Chinese Med, Dept Hepatol, Shenzhen Hosp, Shenzhen, Guangdong, Peoples R China
3.Hunan Univ Tradit Chinese Med, Dept Hepatol, Affiliated Hosp 1, Changsha, Hunan, Peoples R China
4.Hunan Univ Tradit Chinese Med, Affiliated Hosp 1, 113 Middle Shaoshan Rd, Changsha 410007, Hunan, Peoples R China

Zhang, Fan,Zhou, Kun,Yuan, Wei,et al. Radix Bupleuri-Radix Paeoniae Alba Inhibits the Development of Hepatocellular Carcinoma through Activation of the PTEN/PD-L1 Axis within the Immune Microenvironment[J]. NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL,2023.

Zhang, Fan,Zhou, Kun,Yuan, Wei,&Sun, Kewei.(2023).Radix Bupleuri-Radix Paeoniae Alba Inhibits the Development of Hepatocellular Carcinoma through Activation of the PTEN/PD-L1 Axis within the Immune Microenvironment.NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL.

Zhang, Fan,et al."Radix Bupleuri-Radix Paeoniae Alba Inhibits the Development of Hepatocellular Carcinoma through Activation of the PTEN/PD-L1 Axis within the Immune Microenvironment".NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL (2023).