ABSTRACT
OBJECTIVE: The aim of this study was to explain the effects of curcumin to depress gastric cancer biological activity by regulation miRNA-21 an in in vitro study. METHODS: Collecting 30 pairs of adjacent and cancer tissues to measure miRNA-21 expression by ISH, evaluating pathology by H&E staining and measuring PTEN protein expression by IHC. Evaluating curcumin anti-tumor and correlation between curcumin and miRNA-21 in gastric cancer cell line (AGS) biological activities by CCK-8, flow cytometry, transwell, scratch test, transmission electron microscope, and western blot. RESULTS: Compared with adjacent normal tissues, the miRNA-21 and PTEN expressions of gastric cancer tissues were significantly different (P < 0.001, respectively). By cell experiments, compared with NC group, the AGS cell proliferation was significantly depressed with significantly increasing cell apoptosis by keeping cell cycle in G1 phase (P < 0.001, respectively), and AGS cell invasion and migration were significantly down-regulated (P < 0.001, respectively) in Cur and Cur+BL groups. However, with miRNA-21 supplementation, the AGS cell biological activities were significantly recovered (P < 0.001, respectively). By western blot, compared with the NC group, the PTEN and P21 proteins expressions were significantly up-regulated (P < 0.001, respectively) and the PI3K, AKT, MMP-2 and MMP-9 proteins expressions were significantly down-regulated (P < 0.001, respectively). PTEN, PI3K, AKT, P21, MMP-2 and MMP-9 proteins were significantly decreased with miRNA-21 supplementation (P < 0.001, respectively). CONCLUSION: Curcumin had anti-tumor effects to gastric cancer via ion of miRNA-21 by regulation of the PTEN/PI3K/AKT pathway.
ABSTRACT
Chloramphenicol (Chl) is an effective antimicrobial agent widely used in veterinary medicine and commonly used in fish. Its use is restricted in the clinic because of adverse effects on the immune system and oxidative stress in mammals. However, the effects of Chl treatment on invertebrates remain unclear. Amphioxus, a basal chordate, is an ideal model to study the origin and evolution of the vertebrate immune system as it has a primary vertebrate-like arachidonic acid (AA) metabolic system. Here, we combined transcriptomic and lipidomic approaches to investigate the immune system and observe the oxygenated metabolites of AA to address the antibiotic effects on amphioxus. Tissue necrosis of the gill slits occurred in the Chl-treated amphioxus, but fewer epithelial cells were lost when treated with both Chl and ampicillin (Amp). The immune related pathways were dysregulated in both of the antibiotic treatment groups. The Chl alone treatment resulted in immunosuppression with down-regulation of the innate immune genes. In contrast, the Chl + Amp treatment resulted in immunostimulation to some extent, as shown by KEGG clustering. Furthermore, Chl induced a 3-fold reduction in the level of the eicosanoids, while the Chl + Amp treatment resulted in 1.7-fold increase of eicosanoid level. Thus in amphioxus, Amp might relieve the effects of the Chl-induced immune suppression and increase the level of eicosanoids from AA. Finally, the oxygenated metabolites from AA might be crucial to evaluate the effects of Chl treatment in animals.
ABSTRACT
Eicosanoids play an important role in inducing complex and crucial physiological processes in animals. Eicosanoid biosynthesis in animals is widely reported; however, eicosanoid production in invertebrate tissue is remarkably different to vertebrates and in certain respects remains elusive. We, for the first time, compared the orthologs involved in arachidonic acid (AA) metabolism in 14 species of invertebrates and 3 species of vertebrates. Based on parsimony, a complex AA-metabolic system may have existed in the common ancestor of the Metazoa, and then expanded and diversified through invertebrate lineages. A primary vertebrate-like AA-metabolic system via cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) pathways was further identified in the basal chordate, amphioxus. The expression profiling of AA-metabolic enzymes and lipidomic analysis of eicosanoid production in the tissues of amphioxus supported our supposition. Thus, we proposed that the ancestral complexity of AA-metabolic network diversified with the different lineages of invertebrates, adapting with the diversity of body plans and ecological opportunity, and arriving at the vertebrate-like pattern in the basal chordate, amphioxus.
