双氢青蒿素对人恶性黑色素瘤A375细胞增殖、凋亡和血管生成能力的影响

doi:10.19438/j.cjoms.2026.01.001

摘要/Abstract

摘要： 目的: 探讨双氢青蒿素（dihydroartemisinin,DHA）对人恶性黑色素瘤A375细胞增殖、凋亡及血管生成的影响,并阐明其潜在分子机制。方法: 以人恶性黑色素瘤 A375 细胞为研究对象,设置空白对照组及不同浓度（1、5、10、20、40、80 μmol/L）的DHA处理组。采用CCK-8法检测细胞增殖活性,流式细胞术测定细胞凋亡率,Transwell实验评估细胞侵袭能力,小管形成实验检测血管生成能力,RT-PCR和Western免疫印迹技术分别检测基质金属蛋白酶9（MMP-9）和趋化因子受体4（CXCR4）的mRNA及蛋白表达水平。结果: 与空白组相比,各浓度DHA组的细胞增殖均受到显著抑制,并呈现出剂量依赖性。流式细胞术分析表明,DHA处理组的凋亡细胞数量显著增加,且随药物浓度升高而增多。Transwell实验显示,DHA组中穿透基质膜的细胞数量显著减少。小管形成实验结果表明,DHA能够降低A375细胞的血管生成能力。此外,DHA下调了MMP-9和CXCR4的mRNA及蛋白表达。结论: DHA可能通过下调 MMP-9和CXCR4的表达,抑制人恶性黑色素瘤A375细胞的增殖、侵袭及血管生成,并诱导细胞凋亡。

关键词: 双氢青蒿素, 恶性黑色素瘤, 基质金属蛋白酶9, 趋化因子受体4, 增殖, 细胞凋亡, 血管生成能力

Abstract: PURPOSE: To investigate the effects of dihydroartemisinin(DHA) on the proliferation, apoptosis and angiogenesis of human malignant melanoma A375 cells, and to clarify its potential molecular mechanism. METHODS: Human malignant melanoma A375 cells were used as the research object, and a blank control group and DHA treatment groups with different concentrations (1, 5, 10, 20, 40, 80 μmol/L) were set up. The CCK-8 method was used to detect cell proliferation activity; flow cytometry was used to determine the cell apoptosis rate; Transwell assay was used to evaluate cell invasion ability; tube formation assay was used to detect angiogenesis ability; RT-PCR and Western blot techniques were used to detect the mRNA and protein expression levels of matrix metalloproteinase 9(MMP-9) and chemokine receptor 4 (CXCR4), respectively. RESULTS: Compared with the blank group, cell proliferation in all DHA groups with different concentrations was significantly inhibited in a dose-dependent manner. Flow cytometry analysis showed that the number of apoptotic cells in the DHA-treated groups increased significantly, and it increased with drug concentration. Transwell assay revealed that the number of cells penetrating the matrix membrane in the DHA groups was significantly reduced. The results of tube formation assay indicated that DHA could reduce the angiogenic ability of A375 cells. In addition, DHA down-regulated the mRNA and protein expressions of MMP-9 and CXCR4. CONCLUSIONS: DHA may inhibit the proliferation, invasion and angiogenesis of human malignant melanoma A375 cells and induce cell apoptosis by down-regulating the expressions of MMP-9 and CXCR4.

Key words: Dihydroartemisinin, Malignant melanoma, MMP-9, Chemokine receptor-4, Proliferation, Apoptosis, Angiogenic capacity

中图分类号:

739.8

李帅, 李学敏, 花超超, 李婷, 张宁宁, 赵璐. 双氢青蒿素对人恶性黑色素瘤A375细胞增殖、凋亡和血管生成能力的影响[J]. 中国口腔颌面外科杂志, 2026, 24(1): 1-8.

Li Shuai, Li Xuemin, Hua Chaochao, Li Ting, Zhang Ningning, Zhao Lu. Effect of dihydroartemisinin on proliferation, apoptosis and angiogenic capacity of human malignant melanoma A375 cells[J]. China J Oral Maxillofac Surg, 2026, 24(1): 1-8.

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