甲基原地皂苷(MPD)是一种在萄蕾科根茎中发现的呋喃固醇皂苷，具有降脂和广泛的抗癌特性。然而，MPD在治疗前列腺癌方面的功效尚未被探索。因此，本研究旨在评估MPD在前列腺癌中的抗癌活性和作用机制。通过MTT、伤口愈合、Transwell和流式细胞仪实验证明，MPD抑制了DU145细胞的增殖、迁移、细胞周期和侵袭，并诱导凋亡。在机制上，MPD在胆固醇氧化酶、过氧化物酶和4-氨基苯酚(COD-PAP)检测中降低了胆固醇浓度，随后用蔗糖密度梯度离心分离后，使用免疫荧光和免疫印迹分析检测到破坏了脂质 rafts 。此外，它降低了与丝裂原活化蛋白激酶(MAPK)信号通路有关的蛋白P-细胞外调节蛋白激酶(ERK)的水平，使用免疫印迹分析进行检测。通过预测，MPD诱导了肿瘤抑制器和控制胆固醇代谢的关键因子FOXO1，被预测是MPD的直接靶标。值得注意的是，在体内研究中，MPD显着减小了肿瘤大小，抑制了胆固醇浓度和MAPK信号通路，并在皮下小鼠模型的肿瘤组织中诱导了FOXO1表达和凋亡。这些结果表明，MPD通过诱导FOXO1蛋白，降低胆固醇浓度和破坏脂质 rafts显示抗前列腺癌活性。因此，降低了MAPK信号通路的活性，抑制了癌细胞的增殖、迁移、侵袭和细胞周期，并诱导了前列腺癌细胞的凋亡。

Methyl protodioscin (MPD), a furostanol saponin found in the rhizomes of Dioscoreaceae, has lipid-lowering and broad anticancer properties. However, the efficacy of MPD in treating prostate cancer remains unexplored. Therefore, the present study aimed to evaluate the anticancer activity and action mechanism of MPD in prostate cancer. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound healing, transwell, and flow cytometer assays revealed that MPD suppressed proliferation, migration, cell cycle, and invasion and induced apoptosis of DU145 cells. Mechanistically, MPD decreased cholesterol concentration in the cholesterol oxidase, peroxidase and 4-aminoantipyrine phenol (COD-PAP) assay, disrupting the lipid rafts as detected using immunofluorescence and immunoblot analyses after sucrose density gradient centrifugation. Further, it reduced the associated mitogen-activated protein kinase (MAPK) signaling pathway protein P-extracellular regulated protein kinase (ERK), detected using immunoblot analysis. Forkhead box O (FOXO)1, a tumor suppressor and critical factor controlling cholesterol metabolism, was predicted to be a direct target of MPD and induced by MPD. Notably, in vivo studies demonstrated that MPD significantly reduced tumor size, suppressed cholesterol concentration and the MAPK signaling pathway, and induced FOXO1 expression and apoptosis in tumor tissue in a subcutaneous mouse model. These results suggest that MPD displays anti-prostate cancer activity by inducing FOXO1 protein, reducing cholesterol concentration, and disrupting lipid rafts. Consequently, the reduced MAPK signaling pathway suppresses proliferation, migration, invasion, and cell cycle and induces apoptosis of prostate cancer cells.