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石墨烯通过损害线粒体呼吸来抑制癌细胞的迁移和侵袭。

The inhibition of migration and invasion of cancer cells by graphene via the impairment of mitochondrial respiration.

机构信息

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Biomaterials. 2014 Feb;35(5):1597-607. doi: 10.1016/j.biomaterials.2013.11.020. Epub 2013 Nov 28.

DOI:10.1016/j.biomaterials.2013.11.020
PMID:24290441
Abstract

Graphene and its derivatives have become important nanomaterials worldwide and have potential medical applications including in vivo diagnosis, drug delivery, and photothermal therapy of cancer. However, little is known about their effect on the metastasis of cancer cells, which is the cause of over 90% of patient deaths. In the present investigation, we provide direct evidence that low concentrations of pristine graphene and graphene oxide show no apparent influence on the viability of MDA-MB-231 human breast cancer cells, PC3 human prostate cancer cells, as well as B16F10 mouse melanoma cells. However, both pristine graphene and graphene oxide can effectively inhibit the migration and invasion of these cancer cells. Further studies indicate that exposure of cells to graphene led to the direct inhibition of the electron transfer chain complexes I, II, III and IV, most likely by disrupting electron transfer between iron-sulfur centers, which is due to its stronger ability to accept electrons compared to iron-sulfur clusters through theoretical calculations. The decreased electron transfer chain activity caused a reduction in the production of ATP and subsequent impairment of F-actin cytoskeleton assembly, which is crucial for the migration and invasion of metastatic cancer cells. The inhibition of cancer cell metastasis by graphene and graphene oxide might provide new insights into specific cancer treatment.

摘要

石墨烯及其衍生物已成为全球重要的纳米材料,具有潜在的医学应用,包括体内诊断、药物输送和癌症的光热治疗。然而,人们对它们对癌细胞转移的影响知之甚少,而癌细胞转移是 90%以上患者死亡的原因。在本研究中,我们提供了直接证据,表明原始石墨烯和氧化石墨烯的低浓度对 MDA-MB-231 人乳腺癌细胞、PC3 人前列腺癌细胞以及 B16F10 小鼠黑色素瘤细胞的活力没有明显影响。然而,原始石墨烯和氧化石墨烯都可以有效地抑制这些癌细胞的迁移和侵袭。进一步的研究表明,细胞暴露于石墨烯会直接抑制电子传递链复合物 I、II、III 和 IV,这很可能是通过破坏铁硫中心之间的电子转移来实现的,这是由于其比铁硫簇具有更强的接受电子的能力,这是通过理论计算得出的。电子传递链活性的降低导致 ATP 产量减少,随后破坏了对转移性癌细胞迁移和侵袭至关重要的 F-肌动蛋白细胞骨架组装。石墨烯和氧化石墨烯对癌细胞转移的抑制可能为特定的癌症治疗提供新的见解。

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