Paeoniflorin inhibits hepatocellular carcinoma growth by reducing PD-L1 expression

被引:7
|
作者
Gao, Meng [1 ,2 ]
Zhang, Dongjian [1 ,2 ]
Jiang, Cuihua [1 ,2 ]
Jin, Qiaomei [1 ,2 ]
Zhang, Jian [1 ,2 ,3 ]
机构
[1] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Integrated Tradit Chinese & West, Lab Translat Med, Nanjing 210028, Jiangsu, Peoples R China
[2] Jiangsu Prov Acad Tradit Chinese Med, Lab Translat Med, Nanjing 210028, Jiangsu, Peoples R China
[3] Nanjing Lishui Dist Hosp Tradit Chinese Med, Lab Cent, Nanjing 211200, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Hepatocellular carcinoma; Tumor immunotherapy; Paeoniflorin; PD-L1; SOCS3; IMMUNE-CHECKPOINT BLOCKADE; MACROPHAGES; ACTIVATION; GAMMA; CELLS;
D O I
10.1016/j.biopha.2023.115317
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Abnormal expression of programmed death-ligand 1 (PD-L1) on cancer cells contributes to immune escape in hepatocellular carcinoma (HCC). Paeoniflorin has been shown to inhibit the growth of HCC; however, whether its inhibitory effect involves reducing PD-L1 expression on HCC cells remains unknown. We investigated the antitumor effects of paeoniflorin and its potential regulatory mechanisms in HCC. The effects of paeoniflorin on tumor growth and tumor immunity were determined in H22-xenografted mice and DEN-induced HCC rats. Small interfering RNA against suppressor of cytokine signaling 3 (SOCS3) was transfected into HepG2 cells to verify the effect of paeoniflorin on the SOCS3/signal transducer and activator of transcription 3 (STAT3)/PD-L1signaling pathway. The levels of SOCS3/STAT3/PD-L1 signaling pathway-related mRNAs and proteins were determined by real time-polymerase chain reaction and western blotting, respectively. Interleukin-2 (IL-2), interferon-& gamma; (IFN-& gamma;), granzyme B (GrB), and perforin 1 (PRF1) levels were detected in an H22 and mouse T cell co-culture system. Paeoniflorin can trigger T cell-mediated anti-tumor immune responses by increasing CD8+ T cell counts in tumor tissues, thereby inhibiting tumor growth. Moreover, paeoniflorin increased IL-2, IFN-& gamma;, GrB, and PRF1 levels in the co-culture system. PD-L1 expression was suppressed by paeoniflorin, and this effect was mediated by the SOCS3/STAT3 signaling pathway. Paeoniflorin might thus act via enhancing SOCS3 to inhibit STAT3/PD-L1 signaling and subsequently restore T cell sensitivity to kill tumor cells. Our findings provide novel insights into the anticancer effects of paeoniflorin.
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页数:11
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