SIRT1 mediated gastric cancer progression under glucose deprivation through the FoxO1-Rab7-autophagy axis

PurposeSilent mating type information regulator 2 homolog 1 (SIRT1) and autophagy have a two-way action (promoting cell death or survival) on the progression and treatment of gastric cancer (GC) under different conditions or environments. This study aimed to investigate the effects and underlying mechanism of SIRT1 on autophagy and the malignant biological behavior of GC cells under conditions of glucose deprivation (GD).Materials and methodsHuman immortalized gastric mucosal cell GES-1 and GC cell lines SGC-7901, BGC-823, MKN-45 and MKN-28 were utilized. A sugar-free or low-sugar (glucose concentration, 2.5 mmol/L) DMEM medium was used to simulate GD. Additionally, CCK8, colony formation, scratches, transwell, siRNA interference, mRFP-GFP-LC3 adenovirus infection, flow cytometry and western blot assays were performed to investigate the role of SIRT1 in autophagy and malignant biological behaviors (proliferation, migration, invasion, apoptosis and cell cycle) of GC under GD and the underlying mechanism.ResultsSGC-7901 cells had the longest tolerance time to GD culture conditions, which had the highest expression of SIRT1 protein and the level of basal autophagy. With the extension of GD time, the autophagy activity in SGC-7901 cells also increased. Under GD conditions, we found a close relationship between SIRT1, FoxO1 and Rab7 in SGC-7901 cells. SIRT1 regulated the activity of FoxO1 and upregulated the expression of Rab7 through deacetylation, which ultimately affected autophagy in GC cells. In addition, changing the expression of FoxO1 provided feedback on the expression of SIRT1 in the cell. Reducing SIRT1, FoxO1 or Rab7 expression significantly inhibited the autophagy levels of GC cells under GD conditions, decreased the tolerance of GC cells to GD, enhanced the inhibition of GD in GC cell proliferation, migration and invasion and increased apoptosis induced by GD.ConclusionThe SIRT1-FoxO1-Rab7 pathway is crucial for the autophagy and malignant biological behaviors of GC cells under GD conditions, which could be a new target for the treatment of GC

Efficacy of a formalin-inactivated vaccine against <em>Lactococcus garvieae</em> infection in golden pompano <em>Trachinotus ovatus</em>

*Lactococcus garvieae* is one of the primary pathogens causing the severe disease to golden pompano (*Trachinotus ovatus*). Vaccination is the most effective measure of preventing the occurrence and spread of infectious diseases. However, no commercially available vaccine protects *T. ovatus* against *L. garvieae* infection. In the present study, the formalin-inactivated *L. garvieae* vaccines, consisting of bacterin alone (aqueous vaccine) and combined with oil adjuvant Montanide™ ISA 763 A VG (vaccine+763A), were prepared and administered to *T. ovatus* by intraperitoneal injection. The protective efficacy was evaluated by testing the relative percent survival (RPS), serum enzyme activity, and expression levels of immune-related genes in the tissues of *T. ovatus* after immunization. The results indicated that the relative percentage survival (RPS) values of aqueous vaccine and vaccine+763A were 80% and 90.8% at 8 weeks post-vaccination. The level of antibody titer, lysozyme activities, superoxide dismutase, and catalase in the two vaccinated fish groups increased significantly compared to that in the control group. Moreover, the expression levels of immune-related genes *IgM*, *TNF-α*, *IL-8*, *MHCI-α*, *MHCII*, *CD4*, *CD8α,* and *IL-1β* in all the tested tissues from *T. ovatus* were significantly enhanced after inoculation with aqueous vaccine and vaccine+763A. These findings demonstrated that the developed vaccine combined with oil adjuvant ISA 763 A VG improved immune responses and provided good protective efficacy against *L. garvieae* infection in the golden pompano culture