The Hedgehog (Hh) signaling pathway is involved in a variety of tumor-related diseases, including leukemia. The aim of this study was to determine whether there is an interaction between the Hh signaling pathway and transforming growth factor-β (TGF-β) in the HL60 and U937 cell lines. HL60 and U937 cells were treated with TGF-β, tumor necrosis factor-α (TNF-α) and specific inhibitor of Smad3 (SIS3). The expression of Gli2 was detected by real-time PCR and western blotting. The results showed that TGF-β alone did not affect the Gli2 expression in HL60 cells, while it significantly reduced the level of Gli2 expression in U937 cells. TGF-β+TNF-α reduced the expression of Gli2 in HL60 cells and U937 cells. The reduction in the level of Gli2 expression in U937 cells by TGF-β+TNF-α was greater than that caused by TGF-β alone. SIS3 inhibited the effect of TGF-β. Our results suggest that the effect on Gli2 expression in HL60 and U937 cells induced by TGF-β is Smad3-dependent and independent of Hh receptor signaling.

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