NF-κB downregulation may be involved the depression of tumor cell proliferation mediated by human mesenchymal stem cells  

作　　者：Ling QIAO Tie-jun ZHAO Feng-ze WANG Chang-liang SHAN Li-hong YE Xiao-dong ZHANG 

机构地区：[1]Department of Biochemistry Tianjin Key Laboratory of Mecrobial Functional Genomics, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071, China [2]Department of Cancer Research, Tianjin Key Laboratory of Mecrobial Functional Genomics, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071, China

出　　处：《Acta Pharmacologica Sinica》2008年第3期333-340,共8页中国药理学报（英文版）

基　　金：Project supported in part by grants to Xiaodong ZHANG from the National Basic Research Program of China （973 Program, No 2007CB914800）, National Natural Science Foundation of China （No 30570698）, and Tianjin Natural Scientific Foundation （No 033801211）.Acknowledgements We thank Dr Chuan-shu HUANG （from Nelson Institute of Environmental Medicine, New York University School of Medicine, New York, USA） for providing the pGL-NF-κB and pRL-TK reporter plasmid.

摘　　要：Aim： It has been reported that stem cells are able to home to tumorigenesis and inhibit the proliferation of tumor cells. The purpose of our study was to demonstrate the molecular mechanism of the inhibitory proliferation of hepatoma cells and breast cancer cells mediated by human mesenchymal stem cells （hMSCs）. Methods： The proliferation of H7402 human hepatoma cells and MCF-7 human breast cancer cells was measured by the 5-bromodeoxyuridine （BrdU） incorporation assay and flow cytometry assay after the treatment with conditioned media from hMSCs culture, such as Z3 cells or BMMS-03 cells. The role of NF-κB or the phosphorylation of inhibitor κBα （p-ⅠκBα） in the depression of hepatoma or breast cancer cells treated with conditioned media from Z3 cells or BMMS-03 cells was examined by reporter gene assay, quantitative real-time PCR, and Western blot analysis, respectively. Results： The proliferation of H7402 cells and MCF-7 cells was decreased significantly by the BrdU incorporation assay and flow cytometry assay after treatment. The transcriptional activity and mRNA level of NF-κB were downregulated in the treated cells by reporter gene assay and quantitative realtime PCR in a dose-dependent manner. At the protein level, NF-κB and p-ⅠκBα decreased in the treated cells by Western blot analysis. Conclusion： Conditioned media from hMSCs are able to inhibit the proliferation of tumor cells. NF-κB downregulation is one of reasons for the depression of tumor cell proliferation mediated by hMSCs.Aim： It has been reported that stem cells are able to home to tumorigenesis and inhibit the proliferation of tumor cells. The purpose of our study was to demonstrate the molecular mechanism of the inhibitory proliferation of hepatoma cells and breast cancer cells mediated by human mesenchymal stem cells （hMSCs）. Methods： The proliferation of H7402 human hepatoma cells and MCF-7 human breast cancer cells was measured by the 5-bromodeoxyuridine （BrdU） incorporation assay and flow cytometry assay after the treatment with conditioned media from hMSCs culture, such as Z3 cells or BMMS-03 cells. The role of NF-κB or the phosphorylation of inhibitor κBα （p-ⅠκBα） in the depression of hepatoma or breast cancer cells treated with conditioned media from Z3 cells or BMMS-03 cells was examined by reporter gene assay, quantitative real-time PCR, and Western blot analysis, respectively. Results： The proliferation of H7402 cells and MCF-7 cells was decreased significantly by the BrdU incorporation assay and flow cytometry assay after treatment. The transcriptional activity and mRNA level of NF-κB were downregulated in the treated cells by reporter gene assay and quantitative realtime PCR in a dose-dependent manner. At the protein level, NF-κB and p-ⅠκBα decreased in the treated cells by Western blot analysis. Conclusion： Conditioned media from hMSCs are able to inhibit the proliferation of tumor cells. NF-κB downregulation is one of reasons for the depression of tumor cell proliferation mediated by hMSCs.

关 键 词：mesenchymal stem cells HEPATOMA BREASTCANCER NF-ΚB 

分 类 号：R979.1[医药卫生—药品]