Gadolinium Oxide Nanoparticles Enhance the Cytotoxicity of Chemotherapeutic Drugs by Blocking Autophagic Flux in Human Ovarian Cancer Cells

Background: During chemotherapy, drugs can damage cancer cells’ DNA and cytomembrane structure, and then induce cell death. However, autophagy can increase the chemotherapy resistance of cancer cells, reducing the effect of chemotherapy. Objective: To block the autophagic flux in cancer cells, it is vital to enhance the anti-cancer efficacy of chemotherapy drugs; for this purpose, we test the gadolinium oxide nanoparticles (Gd2O3 NPs)’ effect on autophagy. Methods: The cytotoxicity of Gd2O3 NPs on HeLa cells was evaluated by a (4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide assay. Then, monodasylcadaverine staining, immunofluorescence, immunoblot, and apoptosis assay were conducted to evaluate the effect of Gd2O3 NPs on autophagy and efficacy of chemotherapy drugs in human ovarian cancer cells. Results: We found that Gd2O3 NPs, which have great potential for use as a contrast agent in magnetic resonance imaging, could block the late stage of autophagic flux in a dose-dependent manner and then cause autophagosome accumulation in HeLa cells. When co-treated with 8 μg/mL Gd2O3 NPs and 5 μg/mL cisplatin, the number of dead HeLa cells increased by about 20% compared with cisplatin alone. We observed the same phenomenon in cisplatin-resistant COC1/DDP cells. Conclusion: We conclude that Gd2O3 NPs can block the late stage of autophagic flux and enhance the cytotoxicity of chemotherapeutic drugs in human ovarian cancer cells. Thus, the nanoparticles have significant potential for use in both diagnosis and therapy of solid tumor.