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PD-1/PD-L1 Interaction Upregulates YAP1 Expression in HepG2 Cells Through MAPK/ERK Pathway

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机构: [1]Hosp Chengdu Univ ofTradit Chinese Med, Dept Infect Dis, Chengdu, Sichuan, Peoples R China [2]Shijiazhuang Fifth Hosp, Clin Res Ctr, Shijiazhuang, Hebei, Peoples R China [3]Hebei Med Univ, Hosp 4, Dept Orthoped, Shijiazhuang, Hebei, Peoples R China [4]Hebei Med Univ, Sch Publ Hlth, Shijiazhuang, Hebei, Peoples R China [5]Hosp Chengdu Univ Tradit Chinese Med, Dept Infect Dis, 39 Shi Er Qiao Rd, Chengdu 610072, Sichuan, Peoples R China [6]Shijiazhuang Fifth Hosp, Clin Res Ctr, 42Tanan Rd, Shijiazhuang 050024, Hebei, Peoples R China
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关键词: dihydroartemisinin PD-L1 PD-1 YAP1 ERK liver cancer

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BackgroundAntibodies, which target programmed cell death protein-1 (PD-1) or its ligand programmed death ligand-1 (PD-L1), can rescue T cells from an exhausted state and resume their immune response to cancer cells. Clinically, the purpose of blocking the PD-1/PD-L1 signaling pathway is to induce immune cells to play an anti-tumor role. However, the effect of intertumor PD-1/PD-L1 signal blocking on tumor cells remains unclear.MethodsHepG2 cells were treated with DHA, IFN-gamma, BSA, DDP, PD-1-Fc (1 mu g/ml), IgG-Fc, nivolumab, or human IgG for 24 h, respectively. GEPIA, cBioPortal, and TIMER databases were used to analyze the correlation between YAP1, PD-1, and PD-L1 and ERK, ERK-5, JNK, and p38. Western blot was used to detect the expression of YAP1 and p-ERK.ResultsGEPIA, cBioPortal, and TIMER databases analysis showed that YAP1 was positively correlated with ERK. After HepG2 cells were treated with PD98059 (ERK inhibitor), the expression of YAP1 was decreased. In this study, we investigated the inhibitory effect of PD98059 on PD-1/PD-L1 signaling. Our study found that PD-1-Fc (PD-1 fusion protein) promoted the expression of p-ERK/ERK and YAP1 in HepG2 cells. In contrast, nivolumab (PD-1 blocking antibody) reduced the expression of p-ERK/ERK and YAP1 in IFN-gamma-pretreated HepG2 cells. In addition, the application of DHA also inhibited the expression of p-ERK/ERK to inhibit YAP1. Furthermore, treatment of HepG2 cells with DHA alone or DHA combined with cisplatin (DDP) both inhibited the expression of p-ERK/ERK and YAP1.ConclusionsThese results suggested that PD-1/PD-L1 interactions between tumor cells could promote the expression of ERK or YAP1 within tumors. Moreover, the conduction of PD-1/PD-L1 could be reversed using ERK inhibitors.

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出版当年[2023]版:
大类 | 4 区 医学
小类 | 4 区 药物化学 4 区 食品科技
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大类 | 4 区 医学
小类 | 4 区 药物化学 4 区 食品科技
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出版当年[2023]版:
Q4 CHEMISTRY, MEDICINAL Q4 FOOD SCIENCE & TECHNOLOGY
最新[2024]版:
Q4 CHEMISTRY, MEDICINAL Q4 FOOD SCIENCE & TECHNOLOGY

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第一作者机构: [1]Hosp Chengdu Univ ofTradit Chinese Med, Dept Infect Dis, Chengdu, Sichuan, Peoples R China [2]Shijiazhuang Fifth Hosp, Clin Res Ctr, Shijiazhuang, Hebei, Peoples R China
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通讯机构: [1]Hosp Chengdu Univ ofTradit Chinese Med, Dept Infect Dis, Chengdu, Sichuan, Peoples R China [2]Shijiazhuang Fifth Hosp, Clin Res Ctr, Shijiazhuang, Hebei, Peoples R China [5]Hosp Chengdu Univ Tradit Chinese Med, Dept Infect Dis, 39 Shi Er Qiao Rd, Chengdu 610072, Sichuan, Peoples R China [6]Shijiazhuang Fifth Hosp, Clin Res Ctr, 42Tanan Rd, Shijiazhuang 050024, Hebei, Peoples R China
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