Panaxadiol is a triterpenoid sapogenin monomeric compound found in the roots of Panax ginseng and has a variety of biological activities such as neuroprotective and anti-tumour functions. However, the mechanisms how panaxadiol exerts the anticancer effects remain unknown. The current study aimed to investigate the potential activity of panaxadiol on programmed cell death-ligand 1 (PD-L1) expression and tumour proliferation in human colon cancer cells and to identify the underlying mechanism. Results showed that panaxadiol showed little cytotoxicity as assessed by a cytotoxicity assay and significantly inhibited PD-L1 expression at the protein and mRNA level in a dose-dependent manner. Furthermore, panaxadiol supressed the hypoxia-induced synthesis of hypoxia-inducible factor (HIF)-1α via the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways without affecting HIF-1α degradation. Simultaneously, panaxadiol inhibited STAT3 activation through the JAK1, JAK2, and Src pathways. Moreover, pre-treatment with panaxadiol enhanced the activity of cytotoxic T lymphocytes (CTL) and regained their capacity of tumour cell killing in a T cell and tumour cell co-culture system. Immunoprecipitation showed that panaxadiol inhibited PD-L1 expression by blocking the interaction between HIF-1α and STAT3. The inhibitory effect of panaxadiol on tumour proliferation was further demonstrated by colony formation and EdU labelling assays. The anti-proliferative effect of panaxadiol was also proved by a xenograft assay in vivo. Taken together, the current work highlights the anti-tumour effect of panaxadiol, providing insights into development of cancer therapeutic through PD-L1 inhibition.

中文翻译：

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人参二醇在人结肠癌细胞中通过缺氧诱导因子（HIF）-1α和STAT3抑制程序性细胞死亡配体1表达和肿瘤增殖。

人参二醇是人参根中的三萜类皂甙元单体化合物，具有多种生物活性，例如神经保护和抗肿瘤功能。然而，人参二醇如何发挥抗癌作用的机制仍然未知。当前的研究旨在调查人参二醇对人结肠癌细胞中程序性细胞死亡配体1（PD-L1）表达和肿瘤增殖的潜在活性，并确定其潜在机制。结果显示，人参二醇通过细胞毒性测定显示几乎没有细胞毒性，并且以剂量依赖性方式在蛋白质和mRNA水平上显着抑制PD-L1表达。此外，人参二醇通过磷酸肌醇3激酶（PI3K）和有丝分裂原激活的蛋白激酶（MAPK）途径抑制了低氧诱导的低氧诱导因子（HIF）-1α的合成，而不会影响HIF-1α的降解。同时，人参二醇通过JAK1，JAK2和Src途径抑制STAT3激活。此外，用人参二醇预处理可以增强细胞毒性T淋巴细胞（CTL）的活性，并恢复它们在T细胞和肿瘤细胞共培养系统中杀死肿瘤细胞的能力。免疫沉淀显示人参二醇通过阻断HIF-1α和STAT3之间的相互作用来抑制PD-L1表达。人参二醇对肿瘤增殖的抑制作用通过菌落形成和EdU标记试验进一步证实。人参二醇的抗增殖作用还通过体内异种移植试验证明。