Cytotoxic effect of silica nanoparticles against hepatocellular carcinoma cells through necroptosis induction

二氧化硅纳米颗粒通过诱导坏死性凋亡对肝细胞癌细胞产生细胞毒性作用

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Abstract

Hepatocellular carcinoma (HCC) is a common cancer that affects people worldwide with high morbidity and mortality, and its resistance to current chemotherapeutic drugs is a serious concern. Cytotoxicity of silica nanoparticles (Nano-SiO(2)) towards cancer cells has been reported previously, but the specific mechanism is not fully clear. In this study, Nano-SiO(2) showed a remarkable cytotoxic effect against HCC cells, regardless of whether the cells were drug resistant or not. Further study showed that Nano-SiO(2) treatment leads to cell cycle arrest, apoptosis enhancement and necroptosis induction in the HCC cells. RNA-seq data, together with bioinformatics analysis, revealed that a series of genes involved in cancer cell death could be regulated by Nano-SiO(2), among which ZBP-1 was up-regulated the most by Nano-SiO(2) treatment. The siRNA based experiments demonstrated that ZBP-1 might play a key role in mediating Nano-SiO(2) cytotoxic functions against HCC cells. These results have evidently signified the anti-tumor potential of Nano-SiO(2) in the treatment of HCC.

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