Cisplatin has been reported to promote the expression of programmed cell death ligand-1 (PD-L1) in some cancer cells. However, the underlying mechanism through which PD-L1 is transcriptionally regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p-Akt, p-ERK, and PD-L1 was increased in cisplatin-treated SNU-368 and SNU-739 cells. HGF stimulation also increased PD-L1 expression in these cells. Moreover, Inhibition of HGF/c-MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF-induced PD-L1 expression in SNU-368 and SNU-739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8⁺ T cells in the tumor. Taken together, our study suggested that HGF/c-Met axis-induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin-mediated PD-L1 expression. These findings may provide an alternative avenue for the treatment of HCC.

中文翻译：

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HGF/c-MET 通路有助于顺铂介导的 PD-L1 在肝细胞癌中的表达

据报道，顺铂可促进某些癌细胞中程序性细胞死亡配体 1 (PD-L1) 的表达。然而，PD-L1 在肝细胞癌 (HCC) 细胞中被顺铂转录调节的潜在机制仍然很大程度上未知。在本研究中，我们发现在顺铂处理的 SNU-368 和 SNU-739 细胞中肝细胞生长因子 (HGF)、p-Akt、p-ERK 和 PD-L1 的表达增加。HGF 刺激也增加了这些细胞中 PD-L1 的表达。此外，抑制 HGF/c-MET、PI3K/Akt 和 MEK/ERK 信号通路可以显着阻断顺铂或 HGF 诱导的 SNU-368 和 SNU-739 细胞中的 PD-L1 表达。在体内，PHA665752 与顺铂的组合显着降低了肿瘤重量，CD8 ^{+浸润增加} 肿瘤中的 T 细胞。总之，我们的研究表明，HGF/c-Met 轴诱导 PI3K/Akt 和 MEK/ERK 通路的激活有助于顺铂介导的 PD-L1 表达。这些发现可能为HCC的治疗提供替代途径。