Zn-doped CuO nanocomposites inhibit in vitro and in vivo growth of pancreatic cancer by inducing autophagy through AMPK/mTOR pathway / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE Zn-doped CuO nanocomposites (Zn-CuO NPs) are novel nanoparticles synthesized by our research group.In this study,we assessed the in vitro and in vivo antitumor effects of Zn-CuO NPS on pancreatic cancer cells,as well as the potential mechanisms. METHODS MTS assay was used to detect the effects of Zn-CuO NPS on proliferation pancreatic cancer cells(Panc-mia and Aspc-1). The in vivo antitumor effects of Zn-CuO NPs were detected by xenografts model in nude mice. The effects of Zn-CuO NPS on autophagy were detected bytransmission electron microscopy (TEM) andflow cytometry. Autophagy related proteins were detected by Western blotting. RESULTS Zn-CuO NPS significantly inhibited the proliferation of Panc-mia cells and Aspc-1 cells.In vivo experi-ments showed that Zn-CuO NPS significantly inhibited the tumor growth in nude mice without affecting the body weight of the mice. TEM and flow cytometry showed that Zn-CuO NPS induced autophagy, and significantly increased the number of autophagosome.Western Blot showed that Zn-CuO NPS alterd the expression of autophagy related proteins,such as AMPK,mTORand Beclin-1.Also,AMPK inhibitor could significantly reduce Zn-CuO NPS-induced autophagy pathwayas analyzed byWestern blotting. CONCLUSION The findings suggested that Zn-doped CuO nanocomposites inhibited the in vitro and in vivo growth of pancreatic cancer by inducing autophagy through AMPK/mTOR pathway.