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

血管生成 基质金属蛋白酶 癌症研究 化学 癌细胞 卵巢癌 肿瘤微环境 细胞生物学 癌症 生物 医学 生物化学 内科学 肿瘤细胞
作者
Daomei Chen,Bin Li,Lei Tao,Na Di,Minfang Nie,Yepeng Yang,Congjia,Weibo Xie,Zijuan He,Jiaqiang Wang
出处
期刊:Journal of Nanobiotechnology [Springer Nature]
卷期号:19 (1) 被引量:23
标识
DOI:10.1186/s12951-021-00813-8
摘要

Abstract 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/Cu 2 O composite (CQDs/Cu 2 O) selectively inhibited ovarian cancer SKOV3 cells by targeting cellular microenvironment, such as matrix metalloproteinases, angiogenic cytokines and cytoskeleton. The result was showed CQDs/Cu 2 O possessed anticancer properties against SKOV3 cells with IC 50 = 0.85 μg 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 IC 50 of CQDs/Cu 2 O was approximately 114-fold and 75-fold lower than the IC 50 of commercial artesunate (ART) and oxaliplatin (OXA). Furthermore, CQDs/Cu 2 O 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/Cu 2 O 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/Cu 2 O also regulated angiogenesis-related genes in SKOV3 cells, such as Maspin and TSP1 gene, to suppress angiogenesis. Therefore, CQDs/Cu 2 O selectively mediated of ovarian cancer SKOV3 cells death mainly through decreasing the expression of MMP-2, MMP-9, F-actin, and VEGFR2, meanwhile CQDs/Cu 2 O caused apoptosis of SKOV3 via S phase cell cycle arrest. These findings reveal a new application for the use of CQDs/Cu 2 O composite as potential therapeutic interventions in ovarian cancer SKOV3 cells.
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