Effect Of Hergk~+ Channel Inhibitor E-4031 On The Secretion Of VEGF And Migration Of Leukemia Cells

Objective: To examine the effect of E-4031, the HERG K+ channel specific inhibitor, on VEGF secretion and migration of leukemia cells.Methods: (1) Treat leukemia cells first with E-4031 and measure the secretion of VEGF by leukemia cells with ELISA, using the E-4031 untreated leukemia cells as the control group. Experiments were done in triplicates. (2) Transwell was used to monitor the VEGF-induced migration of K562 leukemia cell lines, leukemia stem cells and primary leukemia cells before/after treatment with E-4031. Experiments were done in quadruplicates.Results: (1) The VEGF secretion of leukemia cells treated with E-4031 was significantly lower than the untreated group (P<0.01). The effect of E-4031 on the secretion of VEGF is prominent in M2. Compared with the control, the treated group's level decreased 94.86%. Secondary is B-ALL(93.38%) and M4(93.0%), and the least is CML(47.76%).(2) The migrating ability of leukemia cells decreased after they were treated with E-4031 (P<0.05). Among the K562 cell line and 10 patients samples, the level of B-All decreased most sharply with74.31%. The two experiments consist well with each other, which demonstrates that E-4031 influences the CLL much more prominent than CML. The secretion of VEGF(pg/L)and the decreased percentage of cell migration number of CLL/CML compared with the control group are 71.91%/47.76% and 68.53%/40% respectively.Conclusion: There should be certain relationship between the activity of HERG K+ channel and the secretion of VEGF. HERG K+ channel may play an important role in the secretion of VEGF and it may affect the migration of leukemia cells. Therefore inhibition of the function of HERG K+ channel may prohibit the secretion of VEGF and the proliferation of leukemia cells. HERG K+ channel might serve as a potential therapeutical target for leukemia.