RESUMEN
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Fig. 4C on p. 6 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, which had already been published. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 24: 685, 2021; DOI: 10.3892/mmr.2021.12325].
RESUMEN
This study sought to investigate the anti-amyloid ß (Aß) and anti-neuroinflammatory effects of catalpol in an Alzheimer's disease (AD) mouse model. METHODS: The effects of catalpol on Aß formation were investigated by thioflavin T assay. The effect of catalpol on generating inflammatory cytokines from microglial cells and the cytotoxicity of microglial cells on HT22 hippocampal cells were assessed by real-time quantitative PCR, ELISA, redox reactions, and cell viability. APPswe/PS1ΔE9 mice were treated with catalpol, and their cognitive ability was investigated using the water maze and novel object recognition tests. Immunohistochemistry and immunofluorescence were used to probe for protein markers of microglia and astrocyte, Aß deposits, and NF-κB pathway activity. Aß peptides, neuroinflammation, and nitric oxide production were examined using ELISA and redox reactions. RESULTS: Catalpol potently inhibited Aß fibril and oligomer formation. In microglial cells stimulated by Aß, catalpol alleviated the expression of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and inducible nitric oxide synthase (iNOS) but promoted the expression of the anti-inflammatory cytokine IL-10. Catalpol alleviated the cytotoxic effects of Aß-exposed microglia on HT22 cells. Treatment with catalpol in APPswe/PS1ΔE9 mice downregulated neuroinflammation production, decreased Aß deposits in the brains and alleviated cognitive impairment. Catalpol treatment decreased the number of IBA-positive microglia and GFAP-positive astrocytes and their activities of the NF-κB pathway in the hippocampus of APPswe/PS1ΔE9 mice. CONCLUSION: The administration of catalpol protected neurons by preventing neuroinflammation and Aß deposits in an AD mouse model. Therefore, catalpol may be a promising strategy for treating AD.
Asunto(s)
Péptidos beta-Amiloides , Disfunción Cognitiva , Medicamentos Herbarios Chinos , Glucósidos Iridoides , Enfermedades Neuroinflamatorias , Fármacos Neuroprotectores , Placa Amiloide , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Glucósidos Iridoides/farmacología , Glucósidos Iridoides/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Placa Amiloide/tratamiento farmacológico , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Animales , Ratones , Modelos Animales de Enfermedad , Citocinas/metabolismo , Línea Celular , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Péptidos beta-Amiloides/antagonistas & inhibidores , Ratones Endogámicos C57BL , Masculino , Femenino , Ratones TransgénicosRESUMEN
Oral squamous cell carcinoma (OSCC) is a cancer associated with high mortality (accounting for 3.1/100,000 deaths per year in Brazil in 2013) and a high frequency of amplification in the expression of the epidermal growth factor receptor (EGFR). Treatment with the EGFR inhibitor cetuximab leads to drug resistance in patients with OSCC due to unknown mechanisms. Galectin3 (Gal3) is a ßgalactoside binding lectin that regulates multiple signaling pathways in cells. The present study aimed to investigate the effect of Gal3 in cetuximabresistant (cetR) OSCC. The OSCC HSC3 cell line was selected to establish a mouse xenograft model, which was treated with cetuximab to induce resistance. Subsequently, a Gal3 inhibitor was used to treat cetR tumors, and the tumor volume was monitored. The expression of Gal3, phosphorylated (p)ERK1/2 and pAkt was assessed using immunohistochemistry. The combined effect of cetuximab and the Gal3 inhibitor on HSC3 tumor xenografts was also investigated. HSC3 cells were cultured in vitro to investigate the regulatory effects of Gal3 on ERK1/2 and Akt via western blotting. In addition, the effects of the Gal3 inhibitor on the proliferation, colony formation, invasion and apoptosis of HSC3 cells were investigated by performing Cell Counting Kit8, colony formation, Transwell and apoptosis assays, respectively. In cetR OSCC tumors, increased expression of Gal3, pERK1/2 and pAkt was observed. Further research demonstrated that Gal3 regulated the expression of both ERK1/2 and Akt in HSC3 cells by promoting phosphorylation. Moreover, the Gal3 inhibitor decreased the proliferation and invasion, but increased the apoptosis of cetR HSC3 cells. In addition, the Gal3 inhibitor suppressed the growth of cetR tumors. Collectively, the results indicated that the Gal3 inhibitor and cetuximab displayed a synergistic inhibitory effect on OSCC tumors. In summary, the present study demonstrated that Gal3 may serve an important role in cetR OSCC. The combination of cetuximab and the Gal3 inhibitor may display a synergistic antitumor effect, thereby inhibiting the development of cetuximab resistance in OSCC.