Selective mediation of ovarian cancer SKOV3 cells death by pristine carbon quantum dots/Cu2O composite through targeting matrix metalloproteinases, angiogenic cytokines and cytoskeleton

被引:40
作者
Chen, Daomei [1 ,2 ]
Li, Bin [2 ]
Lei, Tao [1 ,2 ,3 ]
Na, Di [1 ,2 ,3 ]
Nie, Minfang [1 ,2 ,3 ]
Yang, Yepeng [1 ,2 ,3 ]
Xie, Congjia [1 ,2 ,3 ]
He, Zijuan [1 ,2 ,3 ]
Wang, Jiaqiang [1 ,2 ,3 ]
机构
[1] Yunnan Univ, Sch Mat & Energy, Natl Ctr Int Res Photoelect & Energy Mat, Kunming 650091, Yunnan, Peoples R China
[2] Yunnan Univ, Key Lab Med Chem Nat Resource, Minist Educ, Kunming 650091, Yunnan, Peoples R China
[3] Yunnan Univ, Sch Chem Sci & Technol, Kunming 650091, Yunnan, Peoples R China
基金
中国国家自然科学基金;
关键词
Ovarian cancer SKOV3 cells; Cellular microenvironment; Matrix metalloproteinases; Cytoskeleton; Angiogenesis; MMP-2/9; VEGFR2; F-actin; TUMOR MICROENVIRONMENT; SILVER NANOPARTICLES; INHIBITION; NANOMATERIALS; TOXICITY; INVASION; GENES;
D O I
10.1186/s12951-021-00813-8
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
It was shown that some nanomaterials may have anticancer properties, but lack of selectivity is one of challenges, let alone selective suppression of cancer growth by regulating the cellular microenvironment. Herein, we demonstrated for the first time that carbon quantum dots/Cu2O composite (CQDs/Cu2O) selectively inhibited ovarian cancer SKOV3 cells by targeting cellular microenvironment, such as matrix metalloproteinases, angiogenic cytokines and cytoskeleton. The result was showed CQDs/Cu2O possessed anticancer properties against SKOV3 cells with IC50 = 0.85 mu g mL(-1), which was approximately threefold lower than other tested cancer cells and approximately 12-fold lower than normal cells. Compared with popular anticancer drugs, the IC50 of CQDs/Cu2O was approximately 114-fold and 75-fold lower than the IC50 of commercial artesunate (ART) and oxaliplatin (OXA). Furthermore, CQDs/Cu2O possessed the ability to decrease the expression of MMP-2/9 and induced alterations in the cytoskeleton of SKOV3 cells by disruption of F-actin. It also exhibited stronger antiangiogenic effects than commercial antiangiogenic inhibitor (SU5416) through down-regulating the expression of VEGFR2. In addition, CQDs/Cu2O has a vital function on transcriptional regulation of multiple genes in SKOV3 cells, where 495 genes were up-regulated and 756 genes were down-regulated. It is worth noting that CQDs/Cu2O also regulated angiogenesis-related genes in SKOV3 cells, such as Maspin and TSP1 gene, to suppress angiogenesis. Therefore, CQDs/Cu2O selectively mediated of ovarian cancer SKOV3 cells death mainly through decreasing the expression of MMP-2, MMP-9, F-actin, and VEGFR2, meanwhile CQDs/Cu2O caused apoptosis of SKOV3 via S phase cell cycle arrest. These findings reveal a new application for the use of CQDs/Cu2O composite as potential therapeutic interventions in ovarian cancer SKOV3 cells.
引用
收藏
页数:17
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