Zinc oxide nanoparticles reduce the chemoresistance of gastric cancer by inhibiting autophagy.

BACKGROUND: Gastric cancer (GC) is a common malignancy that results in a high rate of cancer-related mortality. Cisplatin (DDP)-based chemotherapy is the first-line clinical treatment for GC therapy, but chemotherapy resistance remains a severe clinical challenge. Zinc oxide nanoparticle (ZnO-NP) has been identified as a promising anti-cancer agent, but the function of ZnO-NP in GC development is still unclear. AIM: To explore the effect of ZnO-NP on chemotherapy resistance during GC progression. METHODS: ZnO-NP was synthesized, and the effect and underlying mechanisms of ZnO-NP on the malignant progression and chemotherapy resistance of GC cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, colony formation assays, transwell assays, wound healing assays, flow cytometry, and Western blot analysis in GC cells and DDP-resistant GC cells, and by tumorigenicity analyses in nude mice. RESULTS: Our data revealed that ZnO-NP was able to inhibit proliferation, migration, and invasion and induce apoptosis of GC cells. Meanwhile, ZnO-NP significantly reduced the half maximal inhibitory concentration (IC50) of DDP for the inhibition of cell proliferation of DDP-resistant SGC7901/DDP cell lines. Autophagy was increased in DDP-resistant GC cells, as demonstrated by elevated light chain 3-like protein 2 (LC3II)/LC3I and Beclin-1 expression and repressed p62 expression in SGC7901/DDP cells compared to SGC7901 cells. Mechanically, ZnO-NP inhibited autophagy in GC cells and treatment with DDP induced autophagy, which was reversed by ZnO-NP. Functionally, ZnO-NP attenuated the tumor growth of DDP-resistant GC cells in vivo. CONCLUSION: We conclude that ZnO-NP alleviates the chemoresistance of GC cells by inhibiting autophagy. Our findings present novel insights into the mechanism by which ZnO-NP regulates the chemotherapy resistance of GC. ZnO-NP may serve as a potential therapeutic candidate for GC treatment. The potential role of ZnO-NP in the clinical treatment of GC needs clarification in future investigations.

High temperature anionic Fe(III) spin crossover behavior in a mixed-valence Fe(II)/Fe(III) complex.

Two ion-pair Fe(iii) complexes (PPh4)[FeIII(HATD)2]·2H2O (1, H3ATD = azotetrazolyl-2,7-dihydroxynaphthalene) and [FeII(phen)3][FeIII(HATD)2]2·3DMA·3.5H2O (2, phen = 1,10-phenanthroline, DMA = N,N-dimethylformamide) were synthesized by employing the tridentate ligand H3ATD. Crystal structure analyses reveal that complexes 1 and 2 consist of FeIII ions in an octahedral environment where a FeIII ion is coordinated by two HATD2- ligands forming the [FeIII(HATD)2]- core. The shortest cationanion distance between the phosphorus ion of the (PPh4)+ cation and the ferric ion of the [FeIII(HATD)2]- anion is 13.190 Å in complex 1, whereas that between the ferrous ion of the [FeII(Phen)3]2+ cation and the ferric ion of the [FeIII(HATD)2]- anion is 7.821 Å in complex 2. C-HC and C-HO hydrogen interactions between the [FeII(phen)3]2+ cation and the [FeIII(HATD)2]- anion are observed in 2. Face-to-face π-π stacking interactions between naphthalene rings with the separated interplanar center to center distances of 3.421-3.680 Å were observed, which result in a one-dimensional supramolecular chain in complexes 1 and 2. Magnetic measurements show that complex 1 is in the low-spin (LS) state below 500 K, whereas 2 undergoes a high temperature spin crossover (SCO) between 360 and 500 K. Magneto-structural relationship studies reveal that π-stacking, hydrogen interactions and Coulomb interactions between the [FeIII(HATD)2]- anion and the [FeII(phen)3]2+ cation play a crucial role in the high temperature Fe(iii) SCO behaviour of complex 2.