癌细胞趋化因子程序性死亡配体1（PD-L1）的异常表达导致肝细胞癌（HCC）中免疫逃逸。已经证实芍药苷可抑制HCC的生长；然而，其抑制作用是否涉及减少HCC细胞上的PD-L1表达尚不清楚。我们研究了芍药苷在HCC中的抗肿瘤效果及其潜在的调控机制。在H22移植小鼠和DEN诱导的HCC大鼠中确定了芍药苷对肿瘤生长和肿瘤免疫的影响。通过转染抑制细胞因子信号抑制蛋白3（SOCS3）的小分子干扰RNA到HepG2细胞中，验证了芍药苷对SOCS3/信号转导子和活化子3（STAT3）/PD-L1信号通路的影响。采用实时聚合酶链反应和免疫印迹法测定了SOCS3/STAT3/PD-L1信号通路相关的mRNA和蛋白质水平。在H22和小鼠T细胞共培养系统中检测了白细胞介素-2（IL-2）、干扰素-γ（IFN-γ）、颗粒酶B（GrB）和穿孔素1（PRF1）水平。芍药苷能通过增加肿瘤组织中CD8+T细胞的数量来触发T细胞介导的抗肿瘤免疫应答，从而抑制肿瘤生长。此外，芍药苷在共培养系统中增加了IL-2、IFN-γ、GrB和PRF1的水平。芍药苷抑制了PD-L1的表达，并且这一效应是通过SOCS3/STAT3信号通路介导的。因此，芍药苷可能通过增强SOCS3以抑制STAT3/PD-L1信号通路，从而恢复T细胞对肿瘤细胞的敏感性。我们的研究结果为芍药苷的抗癌效应提供了新的见解。© 2023 The Authors. Elsevier Masson SAS出版。保留所有权利。

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-γ (IFN-γ), 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-γ, 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.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.