Institute of Biotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
Department of Urology, Shunde Hospital, Southern Medical University, Guangzhou, China.
Cancer Sci. 2018 Jul;109(7):2109-2118. doi: 10.1111/cas.13639. Epub 2018 Jun 21.
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.
去甲基斑蝥素（NCTD）是一种具有低毒性的有前途的抗肿瘤药物。据报道，它能够调节免疫，但机制尚不清楚。在这里，我们探讨了 NCTD 是否能够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 诱导调节性 T 细胞（Tregs）凋亡并抑制其增殖。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，在用疫苗治疗后，外周血和肿瘤组织中存在更多浸润的肿瘤 Tregs。将 NCTD 加入疫苗治疗中可减少肿瘤浸润 Tregs 的数量，并增加 CD4 和 CD8 T 细胞的数量。与单独使用疫苗相比，NCTD 和疫苗联合治疗更能有效抑制肿瘤生长。总的来说，这是首个报道 NCTD 能够诱导 Tregs 凋亡并增强疫苗诱导的免疫的研究。
