anandamide and Stomach-Neoplasms

Glycerophospholipid signal and fatty acid metabolism are closely related to the occurrence and progression of tumours, and metabolic reprogramming caused by hydrolytic enzymes plays an important role in gastric cancer (GC). Here, we performed whole transcriptome sequencing and combined qRT-PCR to screen out the significantly high expression of fatty acid amide hydrolase (FAAH) in GC tissues, which was further verified in both TCGA and Oncomine databases. Functional tests confirmed that FAAH played an oncogene role in GC, and silencing FAAH could delay tumour growth, inhibit tumour metastasis, and promote cell apoptosis both in vitro and in vivo. FAAH-mediated lipid metabolism reprogramming through coordinated regulation of arachidonoyl ethanolamide (AEA)/lysophosphatidic acid (LPA) signalling and activated the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis to promote GC progression. Luciferase reporter assay and immunofluorescence-fluorescence in situ hybridization (IF-FISH) were applied to validate the interactions of miR-1275/FAAH. Overexpression and knockdown of miR-1275 in vitro could indirectly modulate the above lipid signalling by targeting FAAH, thereby affecting GC progression. Our study indicates that deregulated FAAH is a key lipid signal and the miR-1275/FAAH/AEA/LPA axis can serve as a diagnostic biomarker for GC or as a target for therapy development.

Topics: Cell Line, Tumor; Cell Proliferation; Endocannabinoids; Gene Expression Regulation, Neoplastic; Humans; In Situ Hybridization, Fluorescence; Lipid Metabolism; MicroRNAs; Stomach Neoplasms

Swanson's literature-based discovery focus on resurrecting previously published but neglected knowledge. In this study, we propose a two-step model of the discovery process and generate a hypothesis between anandamide and gastric cancer. Further, the potential relationship was confirmed by follow-up experimentation. The anandamide treatment resulted in cell cycle redistribution of gastric cancer cells. Most importantly, the variation of cell cycle was mediated by some genes from the B-terms of the closed discovery, indicating the potential role of the B-terms. Swanson's literature-based discovery not only collates data for possible interactions, but also provides the potential to observe the larger background behind these direct links and is an invaluable discovery tool for investigators.

Topics: Antineoplastic Agents; Arachidonic Acids; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Computer Simulation; Endocannabinoids; Humans; Knowledge Discovery; Medical Subject Headings; MEDLINE; Polyunsaturated Alkamides; Stomach Neoplasms

Orally applicable Delta9-tetrahydrocannabinol and its synthetic derivatives have been used as antiemetic drugs during chemotherapy in cancer patients. However, it is not well known how cannabinoids influence the effects of chemotherapeutic agents on malignant tumors. In this study, we investigated how the endogenous cannabinoid anandamide (AEA) changes the effect of paclitaxel on gastric cancer cell lines. In the human gastric cancer cell line, HGC-27, which express cannabinoid receptor 1 (CB1), AEA stimulated proliferation at concentrations under 1 microM, while it strongly suppressed proliferation through the induction of apoptosis at 10 microM. This bimodal effect was reproduced by a selective CB1 agonist, arachidonyl-2-chloroethylamide, although the effects were less marked. When AEA was used with paclitaxel, AEA at 10 microM synergistically enhanced the cytotoxic effect of paclitaxel, whereas it showed no significant effect at lower concentrations. Flow cytometric analysis revealed that addition of 10 microM AEA synergistically enhanced paclitaxel-induced apoptosis, possibly through the activation of caspase-3, -8, and -9. Our results suggest that cannabinoids could be a good palliative agent for cancer patients receiving paclitaxel.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Arachidonic Acids; Cannabinoid Receptor Modulators; Caspases; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Drug Synergism; Endocannabinoids; Enzyme Activation; Humans; Paclitaxel; Polyunsaturated Alkamides; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Stomach Neoplasms