Novel Zn-doped CuO nanocomposites inhibit tumor growth in vitro and in vivo:role of reactive oxygen species-dependent apoptosis and autophagy cross-linked by NF-kappaB pathway / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE Zn-doped CuO nanocomposites (nZn-CuO NPs) are novel nanoparticles synthesized by sonochemical method.This study aimed to further investigate the antitumor effects and mechanism of nZn-CuO NPs, as well as the exact mechanism of reactive oxygen species (ROS) on nZn-CuO NPs-induced death using N-acetylcysteine (NAC). METHODS The antitumor effects of nZn-CuO NPs were evaluated by MTS assay and orthotopic transplantation tumor model in nude mice. The effects of nZn-CuO NPs with or without NAC on ROS production, DNA damage, apoptosis, mitochondrial damage, autophagy, lysosome impairment, and ER and Golgi stress were determined. Also,western blot was used to detect apoptosis and autophagy related proteins,as well as NF-κB pathway related proteins. RESULTS nZn-CuO NPs significantly inhibit tumor growth both in vitro and in vivo. nZn-CuO NPs were able to cause cytotoxicity, ROS production, DAN damage mitochondrial damage, apoptosis, and autophagy, and NAC can attenuate them. Further studies showed that nZn-CuO NPs induced changes of apoptosis, autophagy and NF-κB pathway related proteins, and NAC can restore them. CONCLUSION Overall, our data demonstrated that nZn-CuO NPs could inhibit tumor growth both in vitro and in vivo by ROS-dependent regulation of apoptosis and autophagy, which might be cross-linked by NF-κB pathways.