Paclitaxel may inhibit migration and invasion of gastric cancer cells via nod-like receptor family pyrin domain-containing 3/caspase-1/Gasdermin E mediated pyroptosis pathway.

Gastric cancer (GC) is a gastric epithelium-derived malignancy insensitive to post-surgical radiotherapy. Paclitaxel, an anti-microtubule drug, has been proven to induce apoptosis of GC cells; however, its exact mechanism of action is unclear. Therefore, the molecular mechanism by which paclitaxel inhibits the proliferation, migration and invasion of GC cells was investigated in this study. First off, SNU-719 cells were co-cultured with paclitaxel and/or Caspase1 inhibitor VX765. Then the proliferation ability of the cells was detected by MTT after paclitaxel treatment (0, 10, 20, 40, and 80 nM), the migration ability by scratch assay, and the invasion ability by Transwell assay. Next, the levels of interleukin (IL)-1ß and IL-18 in cell culture supernatant were detected by the enzyme linked immunosorbent assay (ELISA). And the level of lactate dehydrogenase (LDH) in the supernatant was measured by a corresponding kit. Finally, western blot was performed to detect the concentrations of Gasdermin E (GSDME), GSDME-N, nod-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, cleaved caspase-1 protein in GC cells. As a result, paclitaxel inhibited the proliferation, migration, and invasion of SNU-719 cells in a concentration-dependent manner. Moreover, it induced the pyroptosis of SNU-719 cells. After cell co-culture with VX765 paclitaxel showed decreased inhibitory effect on the migration and invasion of SNU-719 cells. VX765, additionally, suppressed the NLRP3/caspase-1/GSDME mediated pyroptosis pathway activated by paclitaxel. In a nutshell, paclitaxel may inhibit the migration and invasion of GC cells SNU-719 through the NLRP3/caspase-1/GSDME mediated pyroptosis pathway.

Proteomic study of hypothalamus in pigs exposed to heat stress.

BACKGROUND: With evidence of warming climates, it is important to understand the effects of heat stress in farm animals in order to minimize production losses. Studying the changes in the brain proteome induced by heat stress may aid in understanding how heat stress affects brain function. The hypothalamus is a critical region in the brain that controls the pituitary gland, which is responsible for the secretion of several important hormones. In this study, we examined the hypothalamic protein profile of 10 pigs (15 ± 1 kg body weight), with five subjected to heat stress (35 ± 1 °C; relative humidity = 90%) and five acting as controls (28 ± 3 °C; RH = 90%). RESULT: The isobaric tags for relative and absolute quantification (iTRAQ) analysis of the hypothalamus identified 1710 peptides corresponding to 360 proteins, including 295 differentially expressed proteins (DEPs), 148 of which were up-regulated and 147 down-regulated, in heat-stressed animals. The Ingenuity Pathway Analysis (IPA) software predicted 30 canonical pathways, four functional groups, and four regulatory networks of interest. The DEPs were mainly concentrated in the cytoskeleton of the pig hypothalamus during heat stress. CONCLUSIONS: In this study, heat stress significantly increased the body temperature and reduced daily gain of body weight in pigs. Furthermore, we identified 295 differentially expressed proteins, 147 of which were down-regulated and 148 up-regulated in hypothalamus of heat stressed pigs. The IPA showed that the DEPs identified in the study are involved in cell death and survival, cellular assembly and organization, and cellular function and maintenance, in relation to neurological disease, metabolic disease, immunological disease, inflammatory disease, and inflammatory response. We hypothesize that a malfunction of the hypothalamus may destroy the host physical and immune function, resulting in decreased growth performance and immunosuppression in heat stressed pigs.