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Objective: To investigate the biological behavior of stromal cell-derived factor-1 (SDF-1) on multiple myeloma (MM) cell migration and adhesion and it related signaling pathways.
Methods: Expression of adhesion molecules on MM cells of RPMI8226, XG-1 and XG-7 cells was analysed by flow cytometry, the influence of SDF-1 on CD29 and CD49e distribution by immunofluorescence, the effect of SDF-1 on chemotaxis of MM cells by transwell assay. Activation of phosphoinositide-3 kinase (PI3K) in MM cells treated with SDF-1 and by immunoblotting.
Results: 3 strains of MM cell line expressed many adhesion molecule. RPMI8226, XG-7 cells were all high level of expression of CD29 (> 70%). XG-1, XG-7 cells were all high level of expression of CD44 (> 80%), and XG-7 cells was of CD49d (> 90%). In all of 3 strains, the levels of expression of CD49e were low (< 30%). SDF-1 could not upregulate their expression, but could trigger the establishment of polarized morphology of MM cells and the redistribution of CD29 and CD49e. SDF-1 promoted MM cells adhesion to endothelial cells, stimulated phosphorylation of P85 subunit of PI3K in MM cells and induced MM cells migration, which were inhibited by G protein inhibitor PTX and PI3K inhibitor wortmannin.
Conclusion: SDF-1 can promote MM cell adhesion to endothelial cells, trigger establishment of a polarized morphology of MM cells and redistribution of adhesion molecules and induce MM cells migration via PI3K signaling pathway.
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Oncol Lett
June 2018
Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
Afuresertib (AFU), a novel inhibitor of the serine/threonine kinase AKT, has clinical efficacy as a monotherapy against hematological malignancies and is expected to be used in combination with standard therapies for multiple myeloma (MM). To develop a more effective and less toxic combination of immunomodulatory drugs (IMiDs) for therapy, the antitumor effect of sub-optimal doses of AFU, pomalidomide plus dexamethasone (PD), and the AFU-PD combination on MM cells were examined in the present study. Two MM cell lines, XG-7 and U266, with low sensitivity to both PD and AFU monotherapies, were subjected to these combinations and analyzed.
View Article and Find Full Text PDFZhongguo Shi Yan Xue Ye Xue Za Zhi
December 2016
Institute of Radiation and Irradiation Medicine,Academy of Military Medical Sciences,Beijing 100850,China. E-mail:
Objective: To construct a recombinant lentiviral expression vectors carrying MEG3 and to evaluate its effects on XG-7 cell apoptosis.
Methods: A full-length genomic fragment of human MEG3 was cloned from the pcDNA3.0-MEG3 packaging plasmid and was amplified by PCR.
Drug Des Devel Ther
March 2017
Department of Molecular Immunology, Beijing Institute of Basic Medical Sciences.
According to the three-dimensional (3D) complex structure of (hIL-6⋅hIL-6R⋅gp 130) and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD) and MDL Drug Data Report (MDDR), by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically.
View Article and Find Full Text PDFZhongguo Shi Yan Xue Ye Xue Za Zhi
April 2016
Department of Hematology, Ningbo First Hospital, Ningbo 315010, Zhejiang Province, China. E-mail:
Objective: To construct a co-culture system for bone marrow mesenchymal stem cells (BMMSC) and multiple myeloma (MM) cells, and to investigate the effects of co-cultured BMMSC on the migrating and homing of multiple myeloma cells.
Methods: The BMMSC from the transgenic mice with green fluorescent protein (GFP) fetal bone were cultured by adherent screening. A co-culture system of BMMSC and MM cell line XG-7 cells was constracted, the proliferation and apoptosis of cells were determined by trypan blue exclusion and Annexin V/PI, respectively, MDC staining was employed to detect the autophagy.
Zhonghua Xue Ye Xue Za Zhi
September 2013
Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Objective: To construct a co- culture system of mesenchymal stem cells (MSC) and multiple myeloma (MM) cells and investigate the alterations of connexin 43 (CX43) expression and stromal derived growth factor (SDF)- 1α secretion of MSC.
Methods: CX43 expression and SDF- 1α secretion of MM cell lines (RPMI8226) and human primary MM cells were analyzed by western blot and immunofluorescence. Western blot, RT- PCR and immunofluorescence were employed to detect the alterations of CX43 expression and distribution in MSC directly and indirectly co-cultured with myeloma cells.