OBJECTIVE Evidience appears that parthenolide(PN) induces anti-tumor effects by NF-κB signal pathway.MCL3 the derivative of PN,is sesquiterpene lactone synthesized by the group of Professor Pan Xiandao.The study was ...OBJECTIVE Evidience appears that parthenolide(PN) induces anti-tumor effects by NF-κB signal pathway.MCL3 the derivative of PN,is sesquiterpene lactone synthesized by the group of Professor Pan Xiandao.The study was to explore the anti-tumor activity and mechanism of MCL3 in glioma.METHODS The effect of MCL3 on the proliferation of glioma cell lines was examined by MTT assay.Apoptotic activity was investigated by flow cytometry.The Transwell cell invasion assay was used to determine the effect of MCL3 on the G422 cell invasive ability.The effect of MCL3 on the angio.genesis was analyzed by a capillary-like tube formation assay.The subcutaneously transplanted and orthotopic G422 cell xenograft models were used to detect the effect of MCL3 on tumor growth in vivo.The pathological changes were analyzed by H&E staining.Protein level related to the NF-κB signal pathway was dertimined by Western blotting.The effect of MCL3 on the NF-κB transcriptional activity was examined by a dual-luciferase reporter assay.RESULTS The anti-proliferative activity was observed following treatment with MCL3 for 96 h in G422,U-87 MG,U251 and Hs683 cell lines,and the IC50 was 8.94 μmol·L^(-1),6.44 μmol·L^(-1),14.8 μmol·L^(-1),18.9 μmol·L^(-1),respectively.The percentage of apop.totic cells increased in MCL3-treated G422 cells,and the apoptosis rate was 26.4%(the apoptosis rate was 5.68% in control group).MCL3 could inhibit the invasion in G422 cells,and the invasive inhibition rate was 43.63%(P<0.01) at 10.0 μmol·L^(-1).MCL3 inhibited tube formation of EA.hy926 cells,and the inhibitory rate was 81.67%(P<0.01) at 10.0 μmol·kg^(-1).At 40.00 mg·kg^(-1),MCL3 supressed tumor growth by79.03%(P<0.01) in tumor weight in subcutaneously transplanted G422 xenograft models,and by 69.97%(P<0.01) in volume in orthopotic G422 xenograft models.H&E staining demonstrated that MCL3 could decrease tumor angiogenesis and invasion,increased necrosis of tumor cells.The dualluciferase reporter assay showed that MCL3 inhibited NF-κB transcriptional actvity,and the inhibition rate was 50.07%(P<0.05) at 10.0 μmol·L^(-1) compared with control.Moreover,MCL3 inhibited the phos.phorylation of NF-κB in nuclear mediated by supression of phosphorylated IKKα/β and IκB,and decreased the expression of IL-6 regulated by NF-κB.Eventually,the phosphorylation of State3 decreased following the administration of MCL3,resulting in the downregulation of State3 taget genes,including HIF,VEGF,FAK,MMP-2,MMP-9,Bcl-2 and Bcl-xL.CONCLUSION The anti-tumor effect of MCL3 was partly due to the inhibition of NF-κB/IL-6/State3 pathway in glioma.展开更多
In order to characterize the effects of 17β estradiol （17β-E2） on the expression of IL-6, IL-11 and NF-κB in the human MG-63 osteohlast-like cell line, the expression of IL-6 was detected by RT-PCR, Northern blot...In order to characterize the effects of 17β estradiol （17β-E2） on the expression of IL-6, IL-11 and NF-κB in the human MG-63 osteohlast-like cell line, the expression of IL-6 was detected by RT-PCR, Northern blot and Western blot. The expression of IL-11 was determined by RTPCR, and NF-κB by Western blot. The results showed that 17β-E2 down-regulated the expression of IL-6 mRNA and protein, IL-11 mRNA and NF-κB protein in MG-63 cells. It was suggested that the expression of NF-κB, IL-6 and IL-11 in MG-63 cells could be suppressed by 17β-E2, and this might lend support to estrogen replacement therapy in postmenopausal women.展开更多
文摘OBJECTIVE Evidience appears that parthenolide(PN) induces anti-tumor effects by NF-κB signal pathway.MCL3 the derivative of PN,is sesquiterpene lactone synthesized by the group of Professor Pan Xiandao.The study was to explore the anti-tumor activity and mechanism of MCL3 in glioma.METHODS The effect of MCL3 on the proliferation of glioma cell lines was examined by MTT assay.Apoptotic activity was investigated by flow cytometry.The Transwell cell invasion assay was used to determine the effect of MCL3 on the G422 cell invasive ability.The effect of MCL3 on the angio.genesis was analyzed by a capillary-like tube formation assay.The subcutaneously transplanted and orthotopic G422 cell xenograft models were used to detect the effect of MCL3 on tumor growth in vivo.The pathological changes were analyzed by H&E staining.Protein level related to the NF-κB signal pathway was dertimined by Western blotting.The effect of MCL3 on the NF-κB transcriptional activity was examined by a dual-luciferase reporter assay.RESULTS The anti-proliferative activity was observed following treatment with MCL3 for 96 h in G422,U-87 MG,U251 and Hs683 cell lines,and the IC50 was 8.94 μmol·L^(-1),6.44 μmol·L^(-1),14.8 μmol·L^(-1),18.9 μmol·L^(-1),respectively.The percentage of apop.totic cells increased in MCL3-treated G422 cells,and the apoptosis rate was 26.4%(the apoptosis rate was 5.68% in control group).MCL3 could inhibit the invasion in G422 cells,and the invasive inhibition rate was 43.63%(P<0.01) at 10.0 μmol·L^(-1).MCL3 inhibited tube formation of EA.hy926 cells,and the inhibitory rate was 81.67%(P<0.01) at 10.0 μmol·kg^(-1).At 40.00 mg·kg^(-1),MCL3 supressed tumor growth by79.03%(P<0.01) in tumor weight in subcutaneously transplanted G422 xenograft models,and by 69.97%(P<0.01) in volume in orthopotic G422 xenograft models.H&E staining demonstrated that MCL3 could decrease tumor angiogenesis and invasion,increased necrosis of tumor cells.The dualluciferase reporter assay showed that MCL3 inhibited NF-κB transcriptional actvity,and the inhibition rate was 50.07%(P<0.05) at 10.0 μmol·L^(-1) compared with control.Moreover,MCL3 inhibited the phos.phorylation of NF-κB in nuclear mediated by supression of phosphorylated IKKα/β and IκB,and decreased the expression of IL-6 regulated by NF-κB.Eventually,the phosphorylation of State3 decreased following the administration of MCL3,resulting in the downregulation of State3 taget genes,including HIF,VEGF,FAK,MMP-2,MMP-9,Bcl-2 and Bcl-xL.CONCLUSION The anti-tumor effect of MCL3 was partly due to the inhibition of NF-κB/IL-6/State3 pathway in glioma.
文摘In order to characterize the effects of 17β estradiol （17β-E2） on the expression of IL-6, IL-11 and NF-κB in the human MG-63 osteohlast-like cell line, the expression of IL-6 was detected by RT-PCR, Northern blot and Western blot. The expression of IL-11 was determined by RTPCR, and NF-κB by Western blot. The results showed that 17β-E2 down-regulated the expression of IL-6 mRNA and protein, IL-11 mRNA and NF-κB protein in MG-63 cells. It was suggested that the expression of NF-κB, IL-6 and IL-11 in MG-63 cells could be suppressed by 17β-E2, and this might lend support to estrogen replacement therapy in postmenopausal women.
