Tsai Ming-Yen, Lu Chung-Kuang, Shu Li-Hsin, Liu Hung-Te, Wu Yu-Huei, Lin Yu-Shih, Yang Yao-Hsu, Shih Wei-Tai, Lee I-Yun, Wu Yu-Heng, Wu Ching-Yuan
Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi 613016, Taiwan.
Int J Mol Sci. 2025 Mar 17;26(6):2684. doi: 10.3390/ijms26062684.
Prostate cancer remains a significant global health challenge, necessitating the development of novel therapeutic approaches. This study investigated the therapeutic potential of the formula (XIANZHIFANG formula, XZF), comprising , , , , and , in prostate cancer treatment. HPLC analysis confirmed the presence of key triterpenoids, including Antcin A, B, C, K, and Zhankuic acid B, C, and 4,7-dimethoxy-5-methyl-1,3-benzodioxole. Cytotoxicity assays demonstrated that XZF (50-200 μg/mL) exhibited selective activity, maintaining viability in non-cancerous 293T-cells while enhancing the viability of activated CD8+ and CD4+ T-cells in a dose-dependent manner. XZF significantly reduced PD-1 expression in CD8+ T-cells but not in CD4+ T-cells and inhibited the PD-L1/PD-1 interaction, achieving 93% inhibition at 200 μg/mL. Furthermore, when combined with atezolizumab (1 μg/mL), XZF demonstrated complete blockade of PD-L1/PD-1 interaction. In prostate cancer cells, XZF exhibited differential antiproliferative effects. In PC-3 cells, XZF significantly reduced viability across a concentration range of 25-200 μg/mL, whereas DU145 cells showed only partial inhibition at higher concentrations (100-200 μg/mL). LNCaP cells exhibited a dose-dependent reduction in viability, mirroring the response pattern of PC-3 cells. Conditioned medium from XZF-treated macrophages, particularly human THP-1 cells, significantly suppressed the viability and migration of prostate cancer cells in a dose-dependent manner. Notably, the conditioned medium from XZF-treated THP-1 cells exhibited a stronger inhibitory effect on prostate cancer cell viability and migration compared to murine RAW 264.7 macrophages. These findings indicate that XZF exerts its therapeutic potential through multiple mechanisms, including direct antiproliferative effects on cancer cells, enhancement of T-cell responses, modulation of immune checkpoint pathways, and macrophage-mediated suppression of prostate cancer cell survival and migration. The pronounced effects observed in human macrophage models suggest a promising avenue for further investigation in clinical settings, particularly in combination with existing immunotherapies.
前列腺癌仍然是一项重大的全球健康挑战，因此需要开发新的治疗方法。本研究调查了由[具体成分未给出]组成的仙知方（XIANZHIFANG formula，XZF）在前列腺癌治疗中的潜在治疗作用。高效液相色谱分析证实了关键三萜类化合物的存在，包括茯苓酸A、B、C、K以及展平酸B、C和4,7 - 二甲氧基 - 5 - 甲基 - 1,3 - 苯并二恶唑。细胞毒性试验表明，XZF（50 - 200μg/mL）表现出选择性活性，在非癌性293T细胞中维持细胞活力，同时以剂量依赖方式提高活化的CD8 +和CD4 + T细胞的活力。XZF显著降低CD8 + T细胞中PD - 1的表达，但对CD4 + T细胞无此作用，并抑制PD - L1/PD - 1相互作用，在200μg/mL时抑制率达到93%。此外，当与阿特珠单抗（1μg/mL）联合使用时，XZF显示出对PD - L1/PD - 1相互作用的完全阻断。在前列腺癌细胞中，XZF表现出不同的抗增殖作用。在PC - 3细胞中，XZF在25 - 200μg/mL的浓度范围内显著降低细胞活力，而DU145细胞仅在较高浓度（100 - 200μg/mL）时表现出部分抑制。LNCaP细胞的活力呈现剂量依赖性降低，与PC - 3细胞的反应模式相似。经XZF处理的巨噬细胞（特别是人THP - 1细胞）的条件培养基以剂量依赖方式显著抑制前列腺癌细胞的活力和迁移。值得注意的是，与小鼠RAW 264.7巨噬细胞相比，经XZF处理的THP - 1细胞的条件培养基对前列腺癌细胞活力和迁移的抑制作用更强。这些发现表明，XZF通过多种机制发挥其治疗潜力，包括对癌细胞的直接抗增殖作用、增强T细胞反应、调节免疫检查点途径以及巨噬细胞介导的对前列腺癌细胞存活和迁移的抑制。在人类巨噬细胞模型中观察到的显著效果为在临床环境中进一步研究提供了一个有前景的途径，特别是与现有免疫疗法联合使用时。
