Lin Yan, Guo Tailin, Che Lishuang, Dong Jieqiong, Yu Ting, Zeng Chaiming, Wu Ziyu
Provincial Clinical College of Fujian Medical University, Fuzhou, China.
Department of Geriatric Medicine, Fujian Provincial Hospital, Fuzhou, China.
Mol Carcinog. 2025 Apr;64(4):691-702. doi: 10.1002/mc.23879. Epub 2025 Jan 13.
β-elemene has a variety of anti-inflammatory, antioxidant, and antitumor effects. Currently, the influence of β-elemene on adrenocortical carcinoma (ACC) malignant progression and action mechanism remains unclear. This research aims to explore the influence and action mechanism of β-elemene on ACC progression. The impacts of β-elemene on ACC cell viability, proliferation, migration, and apoptosis were investigated through CCK-8 assay, clone formation assay, Transwell experiment, Wound healing assay, and flow cytometry. The miR-486-3p expression was analyzed utilizing RT-qPCR. According to different databases, neuronal pentraxin 1 (NPTX1) is the predicted downstream target gene of miR-486-3p. Western blot and RT-qPCR were utilized to examine NPTX1 expression. Silencing miR-486-3p or Overexpression NPTX1 in ACC cells further explored whether β-elemene affects ACC cells by regulating miR-486-3p/NPTX1. Finally, a subcutaneous graft tumor model was constructed to investigate how β-elemene may impact tumor growth in vivo. β-elemene decreased the cell viability, hindered cell proliferation and migration capacity, and induced apoptosis of ACC cells. miR-486-3p level in ACC cells was notably reduced in comparison to normal cells, but treatment with β-elemene markedly increased miR-486-3p expression. Additionally, ACC cells showed high level of NPTX1, while miR-486-3p targeted negative regulation of NPTX1. Overexpression miR-486-3p hindered the malignant progression of ACC cells, whereas overexpression NPTX1 reversed the impact of overexpression miR-486-3p. Silencing miR-486-3p or overexpression NPTX1 both attenuated the suppressive influence of β-elemene on the malignant behavior of ACC cells. Additionally, tumor growth was suppressed and apoptosis was induced in tumor cells in vivo by β-elemene. In conclusion, β-elemene reduces ACC cell viability, hinders proliferation and migration, and induces apoptosis through the miR-486-3p/NPTX1 axis.
β-榄香烯具有多种抗炎、抗氧化和抗肿瘤作用。目前，β-榄香烯对肾上腺皮质癌（ACC）恶性进展的影响及其作用机制尚不清楚。本研究旨在探讨β-榄香烯对ACC进展的影响及其作用机制。通过CCK-8法、克隆形成试验、Transwell实验、伤口愈合试验和流式细胞术研究了β-榄香烯对ACC细胞活力、增殖、迁移和凋亡的影响。利用RT-qPCR分析miR-486-3p的表达。根据不同数据库，神经元五聚体蛋白1（NPTX1）是miR-486-3p预测的下游靶基因。采用蛋白质免疫印迹法和RT-qPCR检测NPTX1的表达。在ACC细胞中沉默miR-486-3p或过表达NPTX1，进一步探讨β-榄香烯是否通过调控miR-486-3p/NPTX1影响ACC细胞。最后，构建皮下移植瘤模型，研究β-榄香烯对体内肿瘤生长的影响。β-榄香烯降低了细胞活力，阻碍了细胞增殖和迁移能力，并诱导ACC细胞凋亡。与正常细胞相比，ACC细胞中miR-486-3p水平显著降低，但β-榄香烯处理显著增加了miR-486-3p的表达。此外，ACC细胞显示出高水平的NPTX1，而miR-486-3p靶向负调控NPTX1。过表达miR-486-3p阻碍了ACC细胞的恶性进展，而过表达NPTX1则逆转了过表达miR-486-3p的影响。沉默miR-486-3p或过表达NPTX1均减弱了β-榄香烯对ACC细胞恶性行为的抑制作用。此外，β-榄香烯在体内抑制肿瘤生长并诱导肿瘤细胞凋亡。综上所述，β-榄香烯通过miR-486-3p/NPTX1轴降低ACC细胞活力，阻碍增殖和迁移，并诱导凋亡。
