Objective:Lindqvist-type polyoxometalates(POMs)exhibit potential antitumor activities.This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism.Methods:Using different cancer cell lines,the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains.Cell colony formation assay,autophagy detection,mitochondrial observation,qRT-PCR,Western blotting,and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism.Results:MO-4,a Lindqvist-type POM linking a proline at its side strain,was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells.It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells.Mechanistically,MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species(ROS)levels and resulting in apoptosis.In vivo,breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment.Conclusion:Collectively,the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

目的:明确新型多金属氧酸盐化合物{BiW8O30}对胶质母细胞瘤细胞体内、体外抑制作用的影响,并探讨可能的作用机制.方法:采用不同浓度{BiW8O30}处理LN229、U251细胞.CCK-8法检测细胞增殖能力;细胞划痕和侵袭实验检测细胞迁移和侵袭能力;流式细胞实验检测细胞凋亡情况;DAPI染色观察细胞核形态变化;裸鼠皮下移植瘤模型实验检测肿瘤体内增殖能力;Western blot实验检测细胞中凋亡相关蛋白的表达水平;蛋白质组测序技术分析{BiW8O30}发挥对胶质母细胞瘤细胞抑制作用的可能机制.结果:与对照组相比,{BiW8O30 }处理组的细胞存活率、划痕愈合率、侵袭细胞数均显著降低(P＜0.001).流式细胞实验显示,{BiW8O30}处理提高肿瘤细胞凋亡率(P＜0.05).DAPI染色结果显示,{BiW8O30}处理后,肿瘤细胞出现核浓缩、核碎裂等形态变化.{BiW8O30}处理显著抑制异种移植肿瘤在裸鼠体内的增殖能力(P＜0.05).Western blot结果显示,与对照组相比,{BiW8O30}处理组凋亡相关蛋白XIAP表达降低(P＜0.001),caspase 3表达升高(P＜0.001).蛋白质组测序分析显示,{ BiW8O30 }处理后胶质母细胞瘤细胞内共有559个蛋白的表达出现显著差异,其中250个蛋白上调,309个蛋白下调(符合adj.P-value＜0.05,| Fold change|＞1.5).通过基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,发现差异蛋白主要富集于程序性细胞死亡的调控、细胞凋亡过程、细胞运动的调节、细胞黏附等通路.结论:{ BiW8O30}抑制胶质母细胞瘤细胞体内、体外的增殖能力,体外迁移和侵袭能力,并可诱导肿瘤细胞凋亡,其机制可能与细胞凋亡过程、细胞黏附与运动等通路相关.