Norcantharidin enhances antitumor immunity of GM-CSF prostate cancer cells vaccine by inducing apoptosis of regulatory T cells.
Norcantharidin enhances antitumor immunity of GM-CSF prostate cancer cells vaccine by inducing apoptosis of regulatory T cells.
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去甲斑蝥素通过诱导调节性T细胞凋亡增强GM-CSF前列腺癌细胞疫苗的抗肿瘤免疫
DOI：
10.1111/cas.13639
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发表时间：
2018-07
期刊：
影响因子：
5.7
通讯作者：
Hu Z
中科院分区：
文献类型：
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作者：
Mo L;Zhang X;Shi X;Wei L;Zheng D;Li H;Gao J;Li J;Hu Z
去甲斑蝥素（NCTD）是一种有前途的低毒抗肿瘤药物。据报道能够调节免疫力，但其机制尚不清楚。在这里，我们探讨了NCTD是否可以增强前列腺癌细胞疫苗诱导的抗肿瘤免疫。体外研究结果表明，NCTD 诱导细胞凋亡并抑制调节性 T 细胞 (Treg) 的增殖。机制研究表明，NCTD 抑制 Akt 激活并激活 FOXO1 转录，从而产生促凋亡作用。体内研究结果表明，疫苗治疗后外周血和肿瘤组织中存在更多的肿瘤浸润性Treg。将 NCTD 添加到疫苗治疗中可以减少肿瘤浸润性 Tregs 的数量并增加 CD4+ 和 CD8+ T 细胞的数量。 NCTD 和疫苗的联合治疗比单独使用疫苗更能有效地抑制肿瘤生长。总的来说，这是首次报道NCTD可以诱导Treg细胞凋亡并增强疫苗诱导的免疫力。
Norcantharidin (NCTD) is a promising antitumor drug with low toxicity. It was reported to be able to regulate immunity, but the mechanism is not yet clear. Here we explored whether NCTD could enhance the antitumor immunity induced by prostate cancer cell vaccine. The results of the in vitro study showed that NCTD induced apoptosis and inhibited proliferation of regulatory T cells (Tregs). Mechanistic research showed that NCTD inhibited Akt activation and activated FOXO1 transcription, resulting in a pro‐apoptotic effect. The results of the in vivo study showed that more tumor‐infiltrating Tregs existed within peripheral blood and tumor tissue after treatment with the vaccine. Adding NCTD to vaccine treatment could decrease the number of tumor‐infiltrating Tregs and increase the number of CD4+ and CD8+ T cells. Combination therapy with NCTD and vaccine was more effective in inhibiting tumor growth than the vaccine alone. In general, this is the first report that NCTD could induce apoptosis of Tregs and enhance the vaccine‐induced immunity.
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