Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells.
Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells.
复制标题
氧化亚铜纳米颗粒通过靶向黑色素瘤干细胞抑制黑色素瘤的进展。
DOI：
10.2147/ijn.s130753
复制
发表时间：
2017
影响因子：
8
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Yu B;Wang Y;Yu X;Zhang H;Zhu J;Wang C;Chen F;Liu C;Wang J;Zhu H
近年来的研究表明，金属及其氧化物在抗肿瘤治疗中具有潜在的作用。我们之前的研究表明，氧化亚铜纳米颗粒（CONPs）不仅在体外选择性诱导肿瘤细胞凋亡，而且在小鼠中通过靶向线粒体抑制黑色素瘤的生长和转移，并且对肝脏和肾脏的毒性很小。在进一步的研究中，我们目前的研究发现，CONPs在A375和WM266-4黑色素瘤细胞系中诱导人黑色素瘤干细胞（CD271+/高细胞）凋亡，并能显著抑制参与黑色素瘤干细胞干性维持和肿瘤发生的MITF、SOX10和CD271的表达。通过网格蛋白介导的内吞作用，CD271+/高的细胞比CD271−/低的细胞积累更多的CONPs。此外，低剂量CONPs通过降低SOX10、MITF、CD271和MAPK通路中参与肿瘤进展的基因的表达，降低A375和WM266-4细胞的细胞活力、干性和肿瘤发生，表现出良好的抗黑色素瘤作用。最后，CONPs在荷瘤非肥胖糖尿病-严重联合免疫缺陷（NOD-SCID）小鼠中明显抑制人黑色素瘤的生长，伴肿瘤结构坏死和纤维化，降低CD271、SOX10和MITF的表达。以上结果证明了CONPs通过多种途径，特别是通过靶向黑色素瘤干细胞抑制黑色素瘤进展的有效性。
Recent studies have shown that metal and metal oxide have a potential function in antitumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271+/high cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells. CD271+/high cells could accumulate more CONPs than CD271−/low through clathrin-mediated endocytosis. In addition, lower dosage of CONPs exhibited good anti-melanoma effect by decreasing the cell viability, stemness and tumorigenesis of A375 and WM266-4 cells through reducing the expression of SOX10, MITF, CD271 and genes in MAPK pathway involved in tumor progression. Finally, CONPs obviously suppressed the growth of human melanoma in tumor-bearing nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice, accompanied with tumors structural necrosis and fibrosis remarkably and decreased expression of CD271, SOX10 and MITF. These results above proved the effectiveness of CONPs in inhibiting melanoma progress through multiple pathways, especially through targeting melanoma stem cells.