4.2 Article

Silver nanoparticles achieve cytotoxicity against breast cancer by regulating long-chain noncoding RNA XLOC_006390-mediated pathway

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TOXICOLOGY RESEARCH
卷 10, 期 1, 页码 123-133

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OXFORD UNIV PRESS
DOI: 10.1093/toxres/tfaa090

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silver nanoparticles; breast cancer; lncRNA; microarray; cytotoxicity

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The study revealed the potent cytotoxic effect of silver nanoparticles on breast cancer cells and their ability to sensitize tamoxifen-resistant cells through modulation of long noncoding RNA and miRNA signaling pathways. This provides new insights into the antitumor mechanism of AgNPs and suggests a potential new avenue for drug development using AgNPs.
The specific cytotoxic effect of nanoparticles on tumor cells may be used in future antitumor clinical applications. Silver nanoparticles (AgNPs) have been reported to have potent cytotoxic effect, but the mechanism is unclear. Here, AgNPs were synthesized, and the particle average size was 63.1 +/- 8.3 nm and showed a nearly circular shape, which were determined by transmission electron microscopy and field emission scanning electron microscopy. The selected area electron diffraction patterns showed that the nanoparticles were crystalline. The energy-dispersive X-ray spectrum proved that silver is the main component of nanoparticles. The AgNPs showed potent cytotoxicity in breast cancer cells, no matter whether they were tamoxifen sensitive or resistant. Next, we found that a long noncoding RNA, XLOC_006390, was decreased in AgNPs-treated breast cancer cells, coupled to inhibited cell proliferation, altered cell cycle and apoptotic phenotype. Downstream of AgNPs, XLOC_006390 was recognized to target miR-338-3p and modulate the SOX4 expression. This signaling pathway also mediates the AgNPs function of sensitizing tamoxifen-resistant breast cancer cells to tamoxifen. These results provide a new clue for the antitumor mechanism of AgNPs, and a new way for drug development by using AgNPs.

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