Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, China.
Front Immunol. 2023 Feb 1;14:1070679. doi: 10.3389/fimmu.2023.1070679. eCollection 2023.
In recent years, numerous studies have confirmed that chronic stress is closely related to the development of cancer. Our previous research showed that high levels of stress hormones secreted in the body during chronic stress could inhibit the cancer-killing activity of granulocytes, which could further promote the development of cancer. Therefore, reversing the immunosuppressive effect of stress hormones on granulocytes is an urgent problem in clinical cancer treatment. Here, we selected noradrenaline (NA) as a representative stress hormone.
After screening many traditional Chinese herbal medicine active ingredients, a promising compound, ginsenoside Rg1, attracted our attention. We verified the immunoprotective effect of ginsenoside Rg1 on granulocytes and , and attempted to understand its potential immunoprotective mechanism. We confirmed the immunoprotective effect of ginsenoside Rg1 on granulocytes using cell and animal experiments. Cell counting kit-8 (CCK-8) and experiments were performed to investigate the immunoprotective effects of ginsenoside Rg1 on the anti-cancer function of granulocytes inhibited by NA. Transcriptome sequencing analysis and qRT-PCR showed that NA elevated the mRNA expression of , , , and in granulocytes, thereby reducing the anti-cancer function of granulocytes. In contrast, ginsenoside Rg1 downregulated the mRNA expression of , , , and , and upregulated the mRNA expression of , , , and , thereby enhancing the anti-cancer function of granulocytes inhibited by NA. Transwell cell migration experiments were performed to verify that ginsenoside Rg1 significantly enhanced the migration capability of granulocytes inhibited by NA. Tumor-bearing model mice were used to verify the significant immunoprotective effects . Finally, CCK-8 and hematoxylin and eosin staining experiments indicated that ginsenoside Rg1 exhibited high biosafety and .
In future clinical treatments, ginsenoside Rg1 may be used as an adjuvant agent for cancer treatment to alleviate chronic stress-induced adverse events in cancer patients.
近年来,大量研究证实慢性应激与癌症的发展密切相关。我们之前的研究表明,慢性应激时体内分泌的高水平应激激素可抑制粒细胞的杀伤活性,从而进一步促进癌症的发展。因此,逆转应激激素对粒细胞的免疫抑制作用是临床癌症治疗中亟待解决的问题。在这里,我们选择去甲肾上腺素(NA)作为代表性应激激素。
在筛选了许多中药活性成分后,一种有前途的化合物——人参皂苷 Rg1 引起了我们的注意。我们验证了人参皂苷 Rg1 对粒细胞的免疫保护作用,并试图了解其潜在的免疫保护机制。我们通过细胞和动物实验证实了人参皂苷 Rg1 对粒细胞的免疫保护作用。使用细胞计数试剂盒-8(CCK-8)和实验研究了人参皂苷 Rg1 对被 NA 抑制的粒细胞抗癌功能的免疫保护作用。转录组测序分析和 qRT-PCR 显示,NA 上调了粒细胞中、、和的 mRNA 表达,从而降低了粒细胞的抗癌功能。相比之下,人参皂苷 Rg1 下调了、、和的 mRNA 表达,上调了、、和的 mRNA 表达,从而增强了被 NA 抑制的粒细胞的抗癌功能。Transwell 细胞迁移实验验证了人参皂苷 Rg1 显著增强了被 NA 抑制的粒细胞的迁移能力。荷瘤模型小鼠验证了其显著的免疫保护作用。最后,CCK-8 和苏木精-伊红染色实验表明,人参皂苷 Rg1 表现出较高的生物安全性。
在未来的临床治疗中,人参皂苷 Rg1 可能被用作癌症治疗的辅助剂,以减轻癌症患者慢性应激引起的不良事件。