Rong Zhang1, Zhuogang Liu2, Yingchun Li3, Bin Wu4. 1. Department of Hematology, Shengjing hospital of China Medical University, Shenyang City 110021, China. Electronic address: dr_zhuogangliu@163.com. 2. Department of Hematology, Shengjing hospital of China Medical University, Shenyang City 110021, China. Electronic address: oncology_xj@163.com. 3. Department of Hematology, Shengjing hospital of China Medical University, Shenyang City 110021, China. Electronic address: zhangjin1_sh@126.com. 4. Department of Hematology, Shengjing hospital of China Medical University, Shenyang City 110021, China. Electronic address: drmxl01@163.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our finding suggests that LXR activation regulates leukemic cell fate and biological behavior via SOCS3 pathway, rather than E2F family members.
BACKGROUND: 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. METHODS: Two humanacute 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. RESULTS: 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. CONCLUSION: Our finding suggests that LXR activation regulates leukemic cell fate and biological behavior via SOCS3 pathway, rather than E2F family members.