萝卜硫素通过激活胃癌中的 ΔNP63α/PD-L1 轴来损害免疫检查点阻断疗法。
Sulforaphane impaired immune checkpoint blockade therapy through activating ΔNP63α/PD-L1 axis in gastric cancer.
机构信息
Department of Public Health, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Yinzhou Center for Disease Control and Prevention, Ningbo, China.
出版信息
Mol Carcinog. 2024 Aug;63(8):1611-1620. doi: 10.1002/mc.23749. Epub 2024 May 23.
Sulforaphane (SFN) exerts anticancer effect on various cancers including gastric cancer. However, the regulatory effect of SFN on programmed death-ligand 1 (PD-L1) and checkpoint blockade therapy in gastric cancer have not been elucidated. Here we demonstrated that SFN suppressed gastric cancer cell growth both in vitro and in vivo study. SFN upregulated PD-L1 expression through activating ΔNP63α in gastric cancer cells. Further, we found that SFN impaired the anticancer effect of anti-PD-L1 monoclonal antibody (α-PD-L1 mab) on gastric cancer cells. These results uncover a novel PD-L1 regulatory mechanism and the double-edged role of SFN in gastric cancer intervention.
萝卜硫素（SFN）对包括胃癌在内的多种癌症具有抗癌作用。然而，SFN 对胃癌中程序性死亡配体 1（PD-L1）和检查点阻断治疗的调节作用尚未阐明。在这里，我们证明 SFN 抑制了体外和体内研究中的胃癌细胞生长。SFN 通过激活胃癌细胞中的 ΔNP63α 而上调 PD-L1 表达。此外，我们发现 SFN 削弱了抗 PD-L1 单克隆抗体（α-PD-L1 mab）对胃癌细胞的抗癌作用。这些结果揭示了 PD-L1 调节机制的新发现，以及 SFN 在胃癌干预中的双刃剑作用。
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