Abstract
Zinc doped copper oxide nanocomposites (Zn-CuO NPs) is a novel doped metal nanomaterial synthesized by our group using the sonochemical method. Our previous studies have shown that Zn-CuO NPs could inhibit cancer cell proliferation by inducing apoptosis via ROS-mediated pathway. In the present study, we studied the anticancer effect of Zn-CuO NPs on human pancreatic cancer cells. MTS assay revealed that Zn-CuO NPs was able to inhibit cancer cell growth. TEM, flow cytometry and fluorescence microscope analysis showed that Zn-CuO NPs induced autophagy significantly; the number of autophagosomes increased obviously in cells treated with Zn-CuO NPs. Western blot analysis revealed that treatment with the NPs resulted in activation of AMPK/mTOR pathway in both AsPC-1 and MIA Paca-2 cells in dose dependent manners. Moreover, in the presence of AMPK activator AMPKinone, the protein level of p-AMPK, p-ULK1, Beclin-1 and LC3-II/LC3-I increased, while the protein expression of p-AMPK, p-ULK1, Beclin-1 and LC3-II/LC3-I decreased in the presence of AMPK inhibitor Compound C. In vivo study using xenograft mice revealed that Zn-CuO NPs significantly inhibited tumor growth with low toxicity. Our study confirms that Zn-CuO NPs inhibit the tumor growth both in vitro and in vivo for pancreatic cancer. AMPK/mTOR pathway plays an important role in the NPs induced inhibition of tumor growth.
Highlights
Pancreatic cancer is one of the most fatal diseases around the world with a 5 year survival of approximately 6% (Balachandran et al, 2017; Knudsen et al, 2018)
We firstly examined the effect of Zn-CuO NPs on the viability of several cell lines by MTS assay
The results indicated that AMPK/ULK pathway played an important role in Zn-CuO NPs induced cell autophagy
Summary
Pancreatic cancer is one of the most fatal diseases around the world with a 5 year survival of approximately 6% (Balachandran et al, 2017; Knudsen et al, 2018). Some advances have been made in the treatment of pancreatic cancer by surgery, radiation therapy and chemotherapy in recent years, the 5 year survival rate still remains low (Krempien and Roeder, 2017; Tempero et al, 2017). Zn-CuO NPs Induce Autophagy of Pancreatic Cancer need to explore high-efficient and low-toxic drugs for the treatment of pancreatic cancer. Metal oxide NPs, such as ZnO, CuO, and Fe3O4 NPs have been reported to cause genotoxicity, mitochondrial dysfunction and induce cell apoptosis and autophagy in many cancer cell lines (Baek and An, 2011; Chang et al, 2012; Zhao et al, 2013; Dizaj et al, 2014; Khosravi-Katuli et al, 2018). Our previous study showed that Zn-CuO NPs could inhibit cancer cell proliferation by inducing apoptosis via ROS-mediated pathway (Yuan et al, 2016). We found that the nanomaterials were able to inhibit the glioma both in vitro and in vivo (Wu et al, 2018)
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