Vortioxetine induces apoptosis and autophagy of gastric cancer AGS cells via the PI3K/AKT pathway.

Vortioxetine is a potent antagonist of the 5-hydroxytryptamine receptor and serotonin transporter and has been reported to function as an antidepressant in the treatment of major depressive disorder. However, its antitumor effects remain unclear. Here, we examined whether vortioxetine affects the characteristics of GC cells. Cell viability was measured by a colony formation assay and, in addition, cell invasion, migration and apoptosis assays were performed with a transwell assay and a flow cytometry assay. Protein levels were measured by western blotting. We found that vortioxetine inhibited the proliferation, invasion and migration abilities of AGS cells. Additionally, vortioxetine could induce apoptosis and autophagy by increasing the levels of Bax, active caspase-3/-9, Beclin-1 and light chain 3, as well as by downregulating Bcl-2 and P62. Further investigations indicated that vortioxetine regulated apoptosis and autophagy via activation of the phosphoinositide 3-kinase/AKT pathway. Taken together, our data suggest that vortioxetine has cytotoxic effects against GC AGS cells as a result of inhibiting proliferation, invasion and migration, as well as by inducing apoptosis and autophagy through the phosphoinositide 3-kinase/AKT pathway.

Changes in count and function of splenic lymphocytes from patients with portal hypertension.

AIM: To investigate changes in numbers and proliferative function of splenic lymphocytes in patients with hypersplenism due to portal hypertension (PH), to provide evidence for further study of immune status of the spleen during PH. METHODS: Twelve spleens from patients with hypersplenism due to PH served as the PH group, and four spleens from cases of traumatic spleen rupture were regarded as the control group. After weighing the spleen, lymphocytes were separated and counted using a cell counting plate to calculate the lymphocyte count per gram of spleen tissue (relative quantity) and total lymphocyte count in whole spleen (absolute quantity). The immunohistochemical SP method was used to observe the density and distribution of lymphocytes in the spleen. The MTT method was used to observe changes in lymphocyte proliferative function. RESULTS: As compared to the control group, the splenic lymphocytes in the PH group showed that: (1) There was no difference in distribution but a significant decrease in density; (2) the number of lymphocytes per gram of spleen (relative quantity) decreased significantly [(0.822 +/- 0.157) x 10(8) vs (1.174 +/- 0.254) x 10(8), P < 0.01]; (3) with the significant increase in the weight of the PH spleen (832.6 +/- 278.2 g vs 211.7 +/- 85.6 g, P < 0.01), the total quantity of lymphocytes (absolute quantity) increased significantly [(0.685 +/- 0.072) x 10(11) vs (0.366 +/- 0.057) x 10(11), P < 0.01]; and (4) the proliferative function of lymphocytes was enhanced: T lymphocytes, (0.022 +/- 0.005 vs 0.015 +/- 0.003, P < 0.05), and B lymphocytes (0.034 +/- 0.006 vs 0.023 +/- 0.001, P < 0.01). CONCLUSION: Although lymphocyte density in the spleen decreased in patients with PH, the total quantity of lymphocytes increased because spleen weight increased greatly, along with the proliferating function. With respect to changes in lymphocytes, PH spleens may still have immune function, although it may be disordered. However, complete evaluation of the immune function of the spleen in PH requires more research.