p38 MAPK Contributes to the Growth Inhibition of Leukemic Tumor Cells Mediated by Human Umbilical Cord Mesenchymal Stem Cells

Cellular Physiology and Biochemistry

关键词: Cell cycle arrest;    Mesenchymal stromal cells;    Leukemic tumor cells;    Growth inhibition;    SB203580;    SiRNA;    p38 MAPK;   

DOI  :  10.1159/000323973

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Mesenchymal stem cells (MSCs) have been implicated in antitumor therapy for hematopoietic and non-hematopoietic tumors. Cell-contact and soluble factors are demonstrated to play a role in the growth inhibition of tumor cells mediated by MSCs in vitro, while there is little clue about signaling pathways involved in the process. P38 MAPK has been implicated as a suppressor of cell proliferation and tumorigenesis. We here investigate whether p38 MAPK is involved in MSC-induced growth inhibition of leukemic tumor cells. Methods We characterized the effect of human umbilical cord mesenchymal stem cells (UC-MSCs) on proliferation, cell cycle and phosphorylation pattern of p38 MAPK in HL60 and K562 cells. SB203580, a specific inhibitor of p38 MAPK, or p38 MAPK-small interfering RNA (siRNA), were used to identify the role of p38 in growth suppression by UC-MSCs. We also investigated the expression of cell cycle regulators. Results Treatment with UC-MSCs led to potent proliferation-inhibition of HL60 and K562 cells without inducing apoptosis. Growth inhibition by UC-MSCs was due to G0/G1 arrest. UC-MSCs increased phosphorylation of p38 MAPK in HL60 and K562cells. Pharmacological inhibition or genetic silencing (through siRNA) of p38 MAPK partially abrogated the proliferation-suppression and cell cycle arrest caused by UC-MSCs. UC-MSCs also modulated the expression of cell cycle regulatory proteins in HL60 and K562 cells while SB203580 reversed the effect. Conclusion Taken together, our findings indicate that p38 MAPK is critical for the growth inhibitory effect of UC-MSCs on leukemic tumor cells.

【 授权许可】

CC BY-NC-ND