关键词: 间充质干细胞, 慢性粒细胞白血病, DKK-1, WNT信号通路, RNA干扰

Abstract: Objective To investigate the molecular mechanism of mesenchymal stem cells' inhibitory effect on the proliferation of chronic myeloid leukemia cells K562. The purpose of this research was to provide the basic and clinical rational for leukemia treatment. Methods Adipose-derived mesenchymal stem cells (MSCs) were co-cultured with K562 cells. Then, the proliferation rate of K562 and the gene expression of WNT signaling pathway in K562 were detected using neutralizing antibodies assays, 3H-TdR assays, cell-cycle assays, RNA interference and real-time PCR assays. Results After co-cultured with MSCs, the proliferation rate of K562 was decreased by 77%（P<0.05）, the proportion of K562 cells in G0/G1 phase was significantly higher (62.1%±5.8%) than that (45.2%±6.9%) in K562 cells cultured alone（P<0.05）. And MSC's inhibitory effect was not influenced by the transwell system that prevents the direct interaction of MSCs and K562 cells. We performed neutralizing antibodies assays and found that it was DKK-1 that participated this anti-proliferative process. When the expression of DKK-1 was down-regulated by RNA interference, MSCs' inhibitory effects on K562 cells proliferation were attenuated, and the activity of WNT signaling pathway in K562 cells was partially recovered through detecting the accumulation of β-CATENIN and the expression of c－MYC, CYCLIN D2. Conclusions Adipose-derived MSCs could inhibit the leukemia K562 cells' proliferation by secreting DKK-1, which mediated the suppression effects on WNT signaling pathway of K562 cells and resulted in arresting the cell cycle at G0/G1 phase.

Key words: Mesenchymal stem cells, Chronic Myeloid Leukemia, DKK-1, WNT signaling pathway, RNA interference