放射治疗是前列腺癌（PCa）治疗的基石。然而，其有限的肿瘤敏感性和严重的副作用限制了其临床应用。香菇多糖功能化的硒纳米粒子（LET-SeNPs）在增强放疗敏感性和抗肿瘤活性方面表现出良好的前景。在本研究中，我们研究了 LET-SeNPs 在 PCa 中的放疗增敏机制。我们的结果表明，LET-SeNPs 和 X 射线治疗 (4 Gy) 的组合通过诱导细胞凋亡，显着抑制 PCa 细胞的生长和集落形成，超过了单独治疗的效果。这种组合方法通过 p53、MAPK（丝裂原激活蛋白激酶）和 AKT 途径调节 DNA 损伤。此外，LET-SeNPs 通过下调 TrxR（硫氧还蛋白还原酶）表达并诱导活性氧（ROS）过量产生，增加 PC3 细胞对 X 射线诱导的细胞凋亡的敏感性，从而激活线粒体介导的细胞凋亡信号通路。此外，LET-SeNPs 调节 PARP（聚（ADP-核糖）聚合酶）以防止 DNA 损伤修复。体内研究证实，联合治疗通过协同激活 p53 途径诱导细胞凋亡来抑制 PCa 生长。这些发现凸显了 LET-SeNPs 作为放射治疗增敏剂的潜力，并表明将 LET-SeNPs 与 X 射线治疗相结合，利用硒修饰纳米粒子的抗肿瘤作用，可能是一种有前途的临床应用策略。

Radiation therapy is a cornerstone of prostate cancer (PCa) treatment. However, its limited tumor sensitivity and severe side effects restrict its clinical utility. Lentinan-functionalized selenium nanoparticles (LET-SeNPs) have shown promise in enhancing radiotherapy sensitivity and exhibiting antitumor activity. In this study, we investigated the radiotherapy sensitization mechanism of LET-SeNPs in PCa. Our results demonstrate that the combination of LET-SeNPs and X-ray therapy (4 Gy) significantly inhibited the growth and colony formation of PCa cells by inducing apoptosis, surpassing the effects of individual treatments. This combined approach modulated DNA damage through the p53, MAPK (mitogen-activated protein kinase), and AKT pathways. Furthermore, LET-SeNPs increased PC3 cell sensitivity to X-ray-induced apoptosis by downregulating TrxR (Thioredoxin reductase) expression and inducing reactive oxygen species (ROS) overproduction, thereby activating mitochondria-mediated apoptosis signaling pathways. Additionally, LET-SeNPs regulated PARP (poly (ADP-ribose) polymerase) to prevent DNA damage repair. In vivo studies confirmed that the combination treatment inhibited PCa growth by synergistically activating the p53 pathway to induce cell apoptosis. These findings highlight LET-SeNPs' potential as a radiotherapy sensitizer and suggest that combining LET-SeNPs with X-ray therapy could be a promising strategy for clinical application, leveraging selenium-modified nanoparticles' antitumor effects.