The myelodysplastic syndromes (MDS) are characterized by hemopoietic insufficiency associated with cytopenias leading to serious morbidity and the additional risk of leukemic transformation. Vitamin K2(VK2) is reported to induce apoptosis or differentiation of leukemic cell lines in vitro. For investigating the effects and mechanism of VK2 on human MDS cell line MUTZ-1 in vitro,we observed the changes of morphologic features of MUTZ-1 cells by exposing to VK2.The transmission electron microscope was used to observe the apoptosis of MUTZ-1 cells. Cellular proliferation was determined by the MTT assay. The flow cytometry was used to analysis apoptosis rate and the change of cell cycle. The expression of apoposis-related genes bcl-2, survivin and bax were detected by reverse transcriptase polymerase chain reaction(RT-PCR).The activity of caspase-3 was detected by chemiluminescence assay. After exposing to 10μmol L−1 and higher concentration of VK2, it could inhibit MUTZ-1 cells proliferation in a dose-and time-dependent manner(p<0.05). At concentration of 5μmol/l VK2 treatment, it might accelerate cellular proliferation, but there’s no significant difference compared with control group. Apoptosis peak on FCM and positive Annexin-V FITC/PI on cell membrane showed that VK2 induced apoptosis of MUTZ-1 cells in a dose-and-time-dependent manner, G0/G1 cell cycle arrest, significantly dow-regulated the expression of bcl-2 and survivin, but had no effect on the expression of bax.The activities of caspase-3 were significantly increased. Low concentration of VK2 could facilitate cell proliferation. The higher concentration of VK2 could induce apoptosis of MUTZ-1 cells. These results indicate that VK2 induces MUTZ-1 cells apoptosis by activating caspase-3 pathway, the apoptosis related genes bcl-2, survivin down-regulated might play an important role in this process.
Disclosure: No relevant conflicts of interest to declare.