NF-kappaB downregulation may be involved the depression of tumor cell proliferation mediated by human mesenchymal stem cells.
OBJECTIVE
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-kappaB or the phosphorylation of inhibitor kappaBalpha (p-IkappaBalpha) 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-kappaB were downregulated in the treated cells by reporter gene assay and quantitative real-time PCR in a dose-dependent manner. At the protein level, NF-kappaB and p-IkappaBalpha decreased in the treated cells by Western blot analysis.


CONCLUSIONS
Conditioned media from hMSCs are able to inhibit the proliferation of tumor cells. NF-kappaB downregulation is one of reasons for the depression of tumor cell proliferation mediated by hMSCs.
Qiao
Ling
L
Department of Biochemistry, Tianjin Key Laboratory of Mecrobial Functional Genomics, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Zhao
Tie-jun
TJ
Wang
Feng-ze
FZ
Shan
Chang-liang
CL
Ye
Li-hong
LH
Zhang
Xiao-dong
XD
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000378:metabolism; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics*; D010957:Plasmids; D013997:Time Factors
D017077:Culture Media, Conditioned; D016328:NF-kappa B; D008156:Luciferases; D001973:Bromodeoxyuridine