Paeoniflorin inhibits hepatocellular carcinoma growth by reducing PD-L1 expression
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. W...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223011083 |
| _version_ | 1797686839944937472 |
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| author | Meng Gao Dongjian Zhang Cuihua Jiang Qiaomei Jin Jian Zhang |
| author_facet | Meng Gao Dongjian Zhang Cuihua Jiang Qiaomei Jin Jian Zhang |
| author_sort | Meng Gao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T01:10:29Z |
| format | Article |
| id | doaj.art-27b9253b68cb4f62afad169303c43e12 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-12T01:10:29Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-27b9253b68cb4f62afad169303c43e122023-09-14T04:52:37ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-10-01166115317Paeoniflorin inhibits hepatocellular carcinoma growth by reducing PD-L1 expressionMeng Gao0Dongjian Zhang1Cuihua Jiang2Qiaomei Jin3Jian Zhang4Laboratory of Translational Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Corresponding authors at: Laboratory of Translational Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.Laboratory of Translational Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR ChinaLaboratory of Translational Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR ChinaLaboratory of Translational Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR ChinaLaboratory of Translational Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China; Laboratory of Central, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing 211200, Jiangsu Province, PR China; Corresponding authors at: Laboratory of Translational Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, PR China.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.http://www.sciencedirect.com/science/article/pii/S0753332223011083Hepatocellular carcinomaTumor immunotherapyPaeoniflorinPD-L1SOCS3 |
| spellingShingle | Meng Gao Dongjian Zhang Cuihua Jiang Qiaomei Jin Jian Zhang Paeoniflorin inhibits hepatocellular carcinoma growth by reducing PD-L1 expression Biomedicine & Pharmacotherapy Hepatocellular carcinoma Tumor immunotherapy Paeoniflorin PD-L1 SOCS3 |
| title | Paeoniflorin inhibits hepatocellular carcinoma growth by reducing PD-L1 expression |
| title_full | Paeoniflorin inhibits hepatocellular carcinoma growth by reducing PD-L1 expression |
| title_fullStr | Paeoniflorin inhibits hepatocellular carcinoma growth by reducing PD-L1 expression |
| title_full_unstemmed | Paeoniflorin inhibits hepatocellular carcinoma growth by reducing PD-L1 expression |
| title_short | Paeoniflorin inhibits hepatocellular carcinoma growth by reducing PD-L1 expression |
| title_sort | paeoniflorin inhibits hepatocellular carcinoma growth by reducing pd l1 expression |
| topic | Hepatocellular carcinoma Tumor immunotherapy Paeoniflorin PD-L1 SOCS3 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223011083 |
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