ABSTRACT
AbstractObjective: To investigate the effect of γδ T cells on the proliferation, apoptosis and autophagy of multiple myeloma cells. METHODS: Peripheral blood mononuclear cells (PBMNC) were isolated from healthy volunteers, and stimulated with zoledronic acid (Zol) in combination with rhIL-2. Flow cytometry analysis was used to detected the purity of γδ T cells. γδ T cells were collected and co-cultured with RPMI-8226 or U-266 cells at different effector target ratios. The proliferation of RPMI-8226 or U-266 cell lines were detected by CCK-8. Cell cycle and cell apoptosis were detected by flow cytometry and Western blotï¼The expressions of autophagy-related proteins were detected by Western blot. RESULTS: γδ T cells can be expanded in vitro. γδ T cells could inhibit the proliferation of RPMI-8226 or U-266 cells, induced cell cycle arrest and promoted apoptosis in an effector target-dependent manner. In addition, γδ T cells could induce autophagy of myeloma cells, inhibited the expression of autophagy-related PI3K, P-AKT and P-mTOR, while increased the expression of AMPK and Beclin-1. CONCLUSION: γδ T cells can inhibit the proliferation of RPMI-8226 and U-266 myeloma cells, induce cell cycle arrest, promote apoptosis, and enhance autophagy in vitro. The mechanism may be related to inhibition of PI3K/AKT/mTOR signaling pathway and/or activation of AMPK/Beclin-1 signaling pathway.
Subject(s)
Multiple Myeloma , AMP-Activated Protein Kinases/pharmacology , Apoptosis , Autophagy , Beclin-1/pharmacology , Cell Proliferation , Humans , Leukocytes, Mononuclear/metabolism , Multiple Myeloma/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , T-Lymphocytes , TOR Serine-Threonine Kinases/metabolismABSTRACT
AbstractããAutophagy is a process in which cells in eukaryotes degrades abnormal proteins and organelles, thus it possesses important effects on the survival of normal cells and tumor cells. The related studies have shown that autophagy is widely present in the life activities of myeloma cells, which not only protects myeloma cells, but also induces death, and plays an important role in survival, proliferation, invasion and migration of myeloma cells and the treatment of multiple myeloma. This review focuses on the progress of regulating autophagy in the treatment of multiple myeloma.
Subject(s)
Autophagy , Multiple Myeloma , Apoptosis , Cell Line, Tumor , Cell Proliferation , HumansABSTRACT
Two rhodamine-active probes RBAI (Rhodamine B-di-Aminobenzene-phenyl Isothiocyanate) and RGAI (Rhodamine 6G-di-Aminobenzene-phenyl Isothiocyanate) were designed, synthesized and characterized. The probes were developed as fluorescent and colorimetric chemodosimeters in ethanol-water solution with a broad pH span (5-10) and high selectivity toward Hg2+ but no significant response toward other common competitive cations. The Hg2+-promoted ring opening of spirolactam of the rhodamine moiety induced cyclic guanylation of the thiourea moiety, which resulted in the dual chromo- and fluorogenic observation (off-on). Cytotoxicity and bioimaging studies by L929 living cells and living mice indicated that the probes were negligible cytotoxicity, cell permeable and suitable for detecting Hg2+ in biological environments. Moreover, the new probes not only displayed excellent abilities for the successful detection of Hg2+ in L929 living cells and living mice but also able to detect Hg2+ by adsorbing on solid surfaces and quantitative detection of Hg2+ in real water samples with good recovery (more than 90%), indicating that they have promising prospect for application for Hg2+ sensing in environmental and biological sciences.
Subject(s)
Colorimetry/methods , Fluorescent Dyes/chemistry , Mercury/analysis , Rhodamines/chemical synthesis , Thiocyanates/chemical synthesis , Animals , Cell Line , Cell Survival/drug effects , Crystallography, X-Ray , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/toxicity , Fresh Water/chemistry , Limit of Detection , Mice , Molecular Structure , Rhodamines/chemistry , Rhodamines/pharmacology , Thiocyanates/chemistry , Thiocyanates/pharmacologyABSTRACT
Copper-catalyzed coupling of oxime acetates with aldehydes offers a new strategy for the synthesis of highly substituted pyridines. This novel method tolerates a wide range of functionality and allows for rapid elaboration of the oxime acetates into a variety of substituted pyridines.
