Epstein-Barr virus-latent membrane protein 1 (EBV-LMP1) was associated with lymphoma, but its specific mechanism is still controversial. The study is aimed at studying the regulation of lymphoma resistance by EBV-LMP1 through the MEK1/2/Nrf-2 signaling pathway. First, LMP1 was knocked down in EBV-positive SNK-6 cells and overexpressed in EBV-negative KHYG-1 cells. First, we found that overexpression of LMP1 significantly promoted the resistance of KHYG-1 cells to cisplatin (DDP), which was related to increased autophagy in the cells. In contrast, knockdown of LMP1 expression in SNK-6 cells promoted cellular sensitivity to DDP and reduced the autophagy of cells after DDP treatment. Moreover, specific inhibition of autophagy in KHYG-1 cells significantly attenuated the resistance to DDP caused by overexpression of LMP1, but treatment with rapamycin in SNK-6 cells significantly promoted the autophagy in the cells. Subsequently, overexpression of LMP1 promoted the activation of the MEK1/2-Nrf2 pathway in KYHG-1 cells, whereas knockdown of LMP1 in SNK-6 cells inhibited the activation of the MEK1/2-Nrf2 pathway. Inhibition of MEK1/2/Nrf-2 blocked the promoting effects of LMP1 on lymphoma cell resistance. In conclusion, EBV-LMP1 promotes cell autophagy after DDP treatment by activating the MEK1/2/Nrf-2 signaling pathway in lymphoma cells, thus, enhancing the resistance of lymphoma cells to DDP.

中文翻译：

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Epstein-Barr 病毒潜伏膜蛋白 1 激活 MEK1/2/Nrf-2 信号通路增强 T 细胞淋巴瘤的自噬和顺铂耐药性

爱泼斯坦-巴尔病毒潜伏膜蛋白1（EBV-LMP1）与淋巴瘤相关，但其具体机​​制仍存在争议。本研究旨在研究EBV-LMP1通过MEK1/2/Nrf-2信号通路对淋巴瘤耐药的调控。首先，LMP1 在 EBV 阳性 SNK-6 细胞中被敲低，并在 EBV 阴性 KHYG-1 细胞中过表达。首先，我们发现 LMP1 的过表达显着促进了 KHYG-1 细胞对顺铂 (DDP) 的抗性，这与细胞中自噬增加有关。相比之下，SNK-6 细胞中 LMP1 表达的敲低促进了细胞对 DDP 的敏感性并减少了 DDP 处理后细胞的自噬。此外，对 KHYG-1 细胞自噬的特异性抑制显着减弱了由 LMP1 过表达引起的对 DDP 的抗性，但在 SNK-6 细胞中用雷帕霉素处理显着促进了细胞中的自噬。随后，LMP1 的过表达促进了 KYHG-1 细胞中 MEK1/2-Nrf2 通路的激活，而 SNK-6 细胞中 LMP1 的敲低抑制了 MEK1/2-Nrf2 通路的激活。MEK1/2/Nrf-2 的抑制阻断了 LMP1 对淋巴瘤细胞抗性的促进作用。总之，EBV-LMP1通过激活淋巴瘤细胞中的MEK1/2/Nrf-2信号通路促进DDP处理后的细胞自噬，从而增强淋巴瘤细胞对DDP的抵抗力。MEK1/2/Nrf-2 的抑制阻断了 LMP1 对淋巴瘤细胞抗性的促进作用。总之，EBV-LMP1通过激活淋巴瘤细胞中的MEK1/2/Nrf-2信号通路促进DDP处理后的细胞自噬，从而增强淋巴瘤细胞对DDP的抵抗力。MEK1/2/Nrf-2 的抑制阻断了 LMP1 对淋巴瘤细胞抗性的促进作用。总之，EBV-LMP1通过激活淋巴瘤细胞中的MEK1/2/Nrf-2信号通路促进DDP处理后的细胞自噬，从而增强淋巴瘤细胞对DDP的抵抗力。