Youlin Kuang, Simin Liang, Jian Kang, Li Zhang
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Heliyon. 2023 Mar 29;9(4):e14957. doi: 10.1016/j.heliyon.2023.e14957. eCollection 2023 Apr.
Natural killer (NK) cells play a potent role in antitumor immunity via spontaneously eliminating tumor directly. However, some tumors such as prostate cancer constantly escape this immune response by down-regulating cell surface molecule recognition and/or secreting immune impressive cytokines. Here, we found pterostilbene, a natural agent with potent anticancer activity, could enhance expression of major histocompatibility complex class I chain-related proteins A and B (MICA/B) on prostate cancer cells surface, which are ligands of the natural killer group 2 member D (NKG2D) expressed by NK cells, and inhibit TGF-β1 secretion by prostate cancer cells. Further, we discovered that these effects were caused by inhibition of miR-20a in prostate cancer cells by pterostilbene. MiR-20a could target the 3' untranslated region (UTR) of MICA/B, resulting in their expression down-regulation. Inhibition of TGF-β1 function by its specific antibody attenuated its impairment to NKG2D on NK cells. Finally, we observed that pterostilbene-treated prostate cancer cells were more easily to be killed by NK cells. Taken together, our findings demonstrated inhibition of miR-20a by pterostilbene in prostate cancer cells could increase MICA/B expression and decrease TGF-β1 secretion, which enhanced NK cell-mediated cytotoxicity againt prostate cancer cells, suggesting a potential approach for increasing anti-prostate cancer immune.
自然杀伤（NK）细胞通过直接自发消除肿瘤在抗肿瘤免疫中发挥重要作用。然而，一些肿瘤，如前列腺癌，通过下调细胞表面分子识别和/或分泌免疫抑制性细胞因子，不断逃避这种免疫反应。在这里，我们发现具有强大抗癌活性的天然物质紫檀芪，可以增强前列腺癌细胞表面主要组织相容性复合体I类链相关蛋白A和B（MICA/B）的表达，它们是NK细胞表达的自然杀伤细胞2型成员D（NKG2D）的配体，并抑制前列腺癌细胞分泌转化生长因子-β1（TGF-β1）。此外，我们发现这些作用是由紫檀芪抑制前列腺癌细胞中的miR-20a引起的。MiR-20a可以靶向MICA/B的3'非翻译区（UTR），导致其表达下调。用其特异性抗体抑制TGF-β1功能可减轻其对NK细胞上NKG2D的损伤。最后，我们观察到经紫檀芪处理的前列腺癌细胞更容易被NK细胞杀死。综上所述，我们的研究结果表明，紫檀芪在前列腺癌细胞中抑制miR-20a可增加MICA/B表达并减少TGF-β1分泌，从而增强NK细胞介导的对前列腺癌细胞的细胞毒性，提示这是一种增强抗前列腺癌免疫的潜在方法。
