Zou Yani, Xu Helin, Wu Xiu, Liu Xuesong, Zhao Jianfu
Department of Oncology of the First Affiliated Hospital, Jinan University, Guangzhou 510660, China.
Research Center of Cancer Diagnosis and Therapy, Jinan University, Guangzhou 510632, China.
Pharmaceutics. 2024 Sep 21;16(9):1230. doi: 10.3390/pharmaceutics16091230.
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.
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。香菇多糖功能化硒纳米粒子（LET-SeNPs）在增强放射治疗敏感性和展现抗肿瘤活性方面已显示出前景。在本研究中，我们探究了LET-SeNPs在PCa中的放射增敏机制。我们的结果表明，LET-SeNPs与X射线治疗（4 Gy）联合使用通过诱导细胞凋亡显著抑制了PCa细胞的生长和集落形成，其效果超过了单一治疗。这种联合方法通过p53、丝裂原活化蛋白激酶（MAPK）和AKT信号通路调节DNA损伤。此外，LET-SeNPs通过下调硫氧还蛋白还原酶（TrxR）表达和诱导活性氧（ROS）过量产生，增加了PC3细胞对X射线诱导凋亡的敏感性，从而激活线粒体介导的凋亡信号通路。另外，LET-SeNPs调节聚（ADP-核糖）聚合酶（PARP）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信号通路诱导细胞凋亡来抑制PCa生长。这些发现突出了LET-SeNPs作为放射增敏剂的潜力，并表明将LET-SeNPs与X射线治疗相结合可能是一种有前景的临床应用策略，利用了硒修饰纳米粒子的抗肿瘤作用。
