RESUMO
The exact role of autophagy in breast cancers remains elusive. In this study, we explored the potential functions of autophagy-related 7 (Atg7) in breast cancer cell lines and tissues. Compared to normal breast tissue, a significantly lower expression of Atg7 was observed in triple-negative breast cancer (TNBC), but not other subtypes. A higher Atg7 expression was significantly associated with favorable clinicopathologic factors and better prognostic outcomes in patients with TNBC. Reflecting the clinical and pathologic observations, Atg7 was found to inhibit proliferation and migration, but promotes apoptosis in TNBC cell lines. Furthermore, Atg7 suppressed epithelial-mesenchymal transition through inhibiting aerobic glycolysis metabolism of TNBC cells. These findings provided novel molecular and clinical evidence of Atg7 in modulating the biological behavior of TNBC, thus warranting further investigation.
Assuntos
Proteína 7 Relacionada à Autofagia/metabolismo , Neoplasias de Mama Triplo Negativas , Apoptose/efeitos dos fármacos , Proteína 7 Relacionada à Autofagia/análise , Proteína 7 Relacionada à Autofagia/farmacologia , Mama/química , Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
In this study, the effects of salicylate on spatial learning and memory, through its effects on autophagy and apoptosis, were evaluated in the presence of the PKA inhibitor H-89. Adult male Wistar rats were divided into experimental groups as follows: salicylate (30, 50, 100µg/0.5µl/side, intra-hippocampal; 400mg/kg, intra-peritoneal), donepezil (1mg/kg as a positive control for behavioral effects of salicylate), H-89 (1µl/side of 5 or 20µM), H-89 plus salicylate and H-89 plus donepezil. The Morris water maze test was used for evaluation of spatial learning and memory. The levels of different apoptotic and autophagic biomarkers were evaluated using the western blot technique. Salicylate (100µg/0.5µl/side) significantly reduced the escape latency on training days, increased the percentage of time spent in the target quadrant during the probe trial and reversed the inhibitory effects of H-89 during the process of spatial learning and memory. The behavioral efficacy of salicylate was comparable to that of donepezil. In addition, salicylate significantly decreased the levels of apoptotic proteins, Bax and caspase 3, and increased the Bcl2 levels in all groups. Furthermore, the levels of LC3II and Atg7 were decreased by salicylate. Our study revealed that both systemic and direct intra-hippocampal administration of salicylate can facilitate the spatial learning and memory. Additionally, intra-hippocampal administration of salicylate can reduce apoptotic and autophagic proteins. The antioxidant activity of salicylate might lead to increased pCREB via stimulation of signaling pathways, resulting in reduction of H-89-induced apoptosis and autophagy.