LXR agonist regulates the proliferation and apoptosis of human T-Cell acute lymphoblastic leukemia cells via the SOCS3 pathway.

Recent studies show that Liver X receptors (LXR) activation is involved in the regulation of tumor cell death in solid cancer via E2 factor (E2F) transcription factor or suppressor of cytokine signaling-3 (SOCS3) pathway. However, the effect of LXR activation on leukemic cell fate has not been tested.,Two human acute lymphoblastic leukemia (ALL) cell lines, Jurkat and SupT1, were cultured. Cells were transfected with small-interfering RNA (si-RNA) against SOCS3 and E2F family members (including E2F1, E2F2 and E2F3a) followed by treatment with LXR activator GW3965. The cellular biological behaviors, including proliferation, colony-forming ability and apoptosis were tested afterward.,Activation of LXR by GW3965 significantly decreased the cell proliferation rates and colony-forming abilities in the Jurkat and SupT1 cells, but increased their apoptosis rates. Western blot assay show that GW3965 treatment dramatically up-regulated the SOCS3 protein in both cell lines, without affecting E2F1, E2F2 and F2F3a expression levels. SOCS3 inhibition by si-RNA transfection, instead of E2F1, E2F2 and F2F3a pathway inhibition, abolished the aforementioned effects of LXR activation on Jurkat and SupT1 cells.,Our finding suggests that LXR activation regulates leukemic cell fate and biological behavior via SOCS3 pathway, rather than E2F family members.