High grade gliomas are always the research focus in the field of neurosurgery due to their poor prognosis despite the current standard therapeutic regimen of surgical resection followed by radiation therapy and chemot...High grade gliomas are always the research focus in the field of neurosurgery due to their poor prognosis despite the current standard therapeutic regimen of surgical resection followed by radiation therapy and chemotherapy. Alkylating agent temozolomide has been established as the standard chemotherapy while its resistance inevitable during treatment. This phenomenon seriously influences the prognosis of patients suffering from high grade gliomas. This review aims to elucidate temozolomide chemoresistance mechanisms through three chapters including O^6-methylguanine-DNA methyltransferase(MGMT) methylation, mismatch repair mutation and epigenetic regulation consisting of p21, chromatin and histone, Y-box binding protein-1 and micro RNAs.展开更多
Objective:To explore the relationship of the effect of antioxidant status of patients with malignant gliomas at the time of their admission to a tertiary care hospital and the clinical condition after a post operative...Objective:To explore the relationship of the effect of antioxidant status of patients with malignant gliomas at the time of their admission to a tertiary care hospital and the clinical condition after a post operative follow up over a period of two years.Methods: Several antioxidant enzymes like erythrocytic glutathione reductase,glutathione peroxidase,catalase,superoxide dismutase,plasma ceruloplasmin,antioxidant vitamins A,E and C and lipid peroxidation products like erythrocytic thiobarbituric acid reacting substances and plasma conjugated dienes were analyzed both in controls and glioma patients.Results: It was observed that patients who exhibited an overall higher turnover of antioxidants presented with recurrence.Conclusion: Free radical toxicity may adversely affect the outcome of such cancer patients.展开更多
OBJECTIVE The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo,as well as the potential mechanisms.METHODS First,the model of C6 glioma in Wistar rats w...OBJECTIVE The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo,as well as the potential mechanisms.METHODS First,the model of C6 glioma in Wistar rats was established and verified by hemotoxylin and eosin staining,immunohistochemical staining and magnetic resonance imaging(MRI).Then different doses of lapachol were gavaged and tumor volumes of the C6 glioma were detected by MRI.The effects of lapachol on C6 cell proliferation,apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)/phen-azinemethosulfate(PMS)assay,Hoechst33358 staining,AnnexinⅤ-FITC/PI staining,and comet assay.Effects of lapachol on topoisomeraseⅠ(TOPⅠ)and topoisomeraseⅡ(TOPⅡ)activities were detected by TOPⅠand TOPⅡmediated supercoiled p BR322 DNA relaxation assay.Molecular docking was used to predict the interaction of lapachol-TOPⅠand lapachol-TOPⅡ.TOP I and TOPⅡexpression levels in C6 cells were determined by Enzymelinked immunosorbent assay kits and real-time polymerase chain reaction(RT-PCR).RESULTS The rat C6 glioma model was successfully established.High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats(P<0.05).MTS/PMS assay,Hoechst 33258 staining,AnnexinⅤ-FITC/PI staining,and comet assay showed that lapachol could inhibit proliferation,induce apoptosis and DNA damage of C6 cells in dose dependent manners.Lapachol could inhibit the activities of both TOPⅠandⅡ.Molecular docking showed that lapachol-TOPⅠshowed relatively stronger interaction than that of lapachol-TOPⅡ.Enzyme-linked immunosorbent assay and RT-PCR showed that lapachol could inhibit TOPⅡexpression levels,but not TOPⅠexpression levels.CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro,which might be related with inhibiting TOPⅠand TOPⅡactivities,as wel as TOPⅡexpression.展开更多
OBJECTIVE Lapachol is a natural naphthoquinone compound that possesses extensive biological activities.The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in v...OBJECTIVE Lapachol is a natural naphthoquinone compound that possesses extensive biological activities.The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo,as well as the potential mechanisms.METHODS The antitumor effect of lapachol was firstly evaluated in the C6 glioma model in Wistar rats.The effects of lapachol on C6 cell proliferation,apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)/phenazinemethosulfate(PMS)assay,hoechst 33358 staining,annexinⅤ-FITC/PI staining,and comet assay.Effects of lapachol on topoisomerase I(TOP I)and topoisomeraseⅡ(TOPⅡ)activities were detected by TOPⅠand TOPⅡmediated supercoiled p BR322DNA relaxation assays and molecular docking.TOPⅠand TOPⅡexpression levels in C6 cells were also determined.RESULTS High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats(P<0.05).It was showed that lapachol could inhibit proliferation,induce apoptosis and DNA damage of C6 cel s in dose dependent manners.Lapachol could inhibit the activities of both TOPⅠ and Ⅱ.Lapachol-TOPⅠshowed relatively stronger interaction than that of lapachol-TOPⅡin molecular docking study.Also,lapachol could inhibit TOPⅡexpression levels,but not TOPⅠexpression levels.CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro,which might be related with inhibiting TOPⅠ and TOPⅡ activities,as wel as TOPⅡ expression.展开更多
OBJECTIVE To investigate the effect of gap junctions on the anti-tumor function induced by mi R-34a in glioma U87 cells.METHODS 1.Transfection(miR-34a mimics were transfected into glioma cells to upregulate their expr...OBJECTIVE To investigate the effect of gap junctions on the anti-tumor function induced by mi R-34a in glioma U87 cells.METHODS 1.Transfection(miR-34a mimics were transfected into glioma cells to upregulate their expression);2.Co-culture assay(U87cells were transfected with mi R-34a co-cultured with U87 cells that was transfected PCMV-eG FP plasmid);3.Flow cytometry analysis(select the e GFP labed U87 cells);4.RNA isolation and real-time PCR;5.CCK-8 assay;6.Western blotting.RESULTS Mi R-34a mimics transfered between the U87 cells.Parachute assay showed that GJ inhibition(CBX and 18-α-GA)can decrease mi R-34a expression than co-culture group.RA and galanglin enhanced mi R-34a expression than co-culture group.Mi R-34a relative expression reduced after co-culture,while gap junctions composed of Cx43 were down-regulated by sh RNA.Transfected with mi R-34a mimics reduced the survival of U87 cells in a dose-dependent manner.To more specifically establish the role of GJIC in mi R-34a induced growth inhibition of U87 cells,si RNA was used to knockdown the expression of Cx43,the dominant connexin expressed in U87 cells.CCK-8 assay showed that siR NAs have no effect on cell growth,but they could aggravate the growth inhibition of miR-34a to U87 cels.CONCLUSION Gap junctions enhance the antiproliferative effect of miR NA-34a in glioma cells.展开更多
OBJECTIVE Glioblastoma multiforme(GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiot...OBJECTIVE Glioblastoma multiforme(GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de.veloping new agents to treat GBM is important.This study aimed to evaluate the anti-tumor effect of evodiamine(Evo) on GBM cells,and to determine the underlying mechanisms involved.METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo.diamine(0-10 μmol·L^(-1)) for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS) production was detected using dichlorofluorescein diacetate(DCFH-DA) staining.The changes in mitochondrial mem.brane potential(MMP) were assessed by JC-1 after cells were treated with evodiamine.The expres.sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c,Caspase-3,cleaved Caspase-3,PRAP,and cleaved PARP were measured by Western blot analy.ses.RESULTS According to MTT assay results,Evo significantly inhibited the cell proliferation in a time-and dose-dependent manner.Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species(ROS) production and mitochondrial membrane potential(MMP) disruption.Finally,Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos.phorylation(p38 and JNK,but not ERK) to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas.pase-3,and PARP).CONCLUSION In summary,Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.展开更多
Glioblastoma multiforme (GBM), the most commonprimary malignant brain tumor in adults is associated witha poor prognosis despite aggressive treatment withsurgical tumor debulking, radiation, and chemotherapy.Novel app...Glioblastoma multiforme (GBM), the most commonprimary malignant brain tumor in adults is associated witha poor prognosis despite aggressive treatment withsurgical tumor debulking, radiation, and chemotherapy.Novel approaches including gene therapy provide newalternatives in the treatment of GBM. Apo-2 ligand(Apo-2L), a novel cytokine, is a member of the展开更多
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
基金Scientific Research Project of Science and Technology Committee of Shanghai Municipality, 14DZ1930303
文摘High grade gliomas are always the research focus in the field of neurosurgery due to their poor prognosis despite the current standard therapeutic regimen of surgical resection followed by radiation therapy and chemotherapy. Alkylating agent temozolomide has been established as the standard chemotherapy while its resistance inevitable during treatment. This phenomenon seriously influences the prognosis of patients suffering from high grade gliomas. This review aims to elucidate temozolomide chemoresistance mechanisms through three chapters including O^6-methylguanine-DNA methyltransferase(MGMT) methylation, mismatch repair mutation and epigenetic regulation consisting of p21, chromatin and histone, Y-box binding protein-1 and micro RNAs.
文摘Objective:To explore the relationship of the effect of antioxidant status of patients with malignant gliomas at the time of their admission to a tertiary care hospital and the clinical condition after a post operative follow up over a period of two years.Methods: Several antioxidant enzymes like erythrocytic glutathione reductase,glutathione peroxidase,catalase,superoxide dismutase,plasma ceruloplasmin,antioxidant vitamins A,E and C and lipid peroxidation products like erythrocytic thiobarbituric acid reacting substances and plasma conjugated dienes were analyzed both in controls and glioma patients.Results: It was observed that patients who exhibited an overall higher turnover of antioxidants presented with recurrence.Conclusion: Free radical toxicity may adversely affect the outcome of such cancer patients.
文摘OBJECTIVE The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo,as well as the potential mechanisms.METHODS First,the model of C6 glioma in Wistar rats was established and verified by hemotoxylin and eosin staining,immunohistochemical staining and magnetic resonance imaging(MRI).Then different doses of lapachol were gavaged and tumor volumes of the C6 glioma were detected by MRI.The effects of lapachol on C6 cell proliferation,apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)/phen-azinemethosulfate(PMS)assay,Hoechst33358 staining,AnnexinⅤ-FITC/PI staining,and comet assay.Effects of lapachol on topoisomeraseⅠ(TOPⅠ)and topoisomeraseⅡ(TOPⅡ)activities were detected by TOPⅠand TOPⅡmediated supercoiled p BR322 DNA relaxation assay.Molecular docking was used to predict the interaction of lapachol-TOPⅠand lapachol-TOPⅡ.TOP I and TOPⅡexpression levels in C6 cells were determined by Enzymelinked immunosorbent assay kits and real-time polymerase chain reaction(RT-PCR).RESULTS The rat C6 glioma model was successfully established.High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats(P<0.05).MTS/PMS assay,Hoechst 33258 staining,AnnexinⅤ-FITC/PI staining,and comet assay showed that lapachol could inhibit proliferation,induce apoptosis and DNA damage of C6 cells in dose dependent manners.Lapachol could inhibit the activities of both TOPⅠandⅡ.Molecular docking showed that lapachol-TOPⅠshowed relatively stronger interaction than that of lapachol-TOPⅡ.Enzyme-linked immunosorbent assay and RT-PCR showed that lapachol could inhibit TOPⅡexpression levels,but not TOPⅠexpression levels.CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro,which might be related with inhibiting TOPⅠand TOPⅡactivities,as wel as TOPⅡexpression.
文摘OBJECTIVE Lapachol is a natural naphthoquinone compound that possesses extensive biological activities.The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo,as well as the potential mechanisms.METHODS The antitumor effect of lapachol was firstly evaluated in the C6 glioma model in Wistar rats.The effects of lapachol on C6 cell proliferation,apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)/phenazinemethosulfate(PMS)assay,hoechst 33358 staining,annexinⅤ-FITC/PI staining,and comet assay.Effects of lapachol on topoisomerase I(TOP I)and topoisomeraseⅡ(TOPⅡ)activities were detected by TOPⅠand TOPⅡmediated supercoiled p BR322DNA relaxation assays and molecular docking.TOPⅠand TOPⅡexpression levels in C6 cells were also determined.RESULTS High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats(P<0.05).It was showed that lapachol could inhibit proliferation,induce apoptosis and DNA damage of C6 cel s in dose dependent manners.Lapachol could inhibit the activities of both TOPⅠ and Ⅱ.Lapachol-TOPⅠshowed relatively stronger interaction than that of lapachol-TOPⅡin molecular docking study.Also,lapachol could inhibit TOPⅡexpression levels,but not TOPⅠexpression levels.CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro,which might be related with inhibiting TOPⅠ and TOPⅡ activities,as wel as TOPⅡ expression.
基金The project supported by National Natural Science Foundation of China(81473234)
文摘OBJECTIVE To investigate the effect of gap junctions on the anti-tumor function induced by mi R-34a in glioma U87 cells.METHODS 1.Transfection(miR-34a mimics were transfected into glioma cells to upregulate their expression);2.Co-culture assay(U87cells were transfected with mi R-34a co-cultured with U87 cells that was transfected PCMV-eG FP plasmid);3.Flow cytometry analysis(select the e GFP labed U87 cells);4.RNA isolation and real-time PCR;5.CCK-8 assay;6.Western blotting.RESULTS Mi R-34a mimics transfered between the U87 cells.Parachute assay showed that GJ inhibition(CBX and 18-α-GA)can decrease mi R-34a expression than co-culture group.RA and galanglin enhanced mi R-34a expression than co-culture group.Mi R-34a relative expression reduced after co-culture,while gap junctions composed of Cx43 were down-regulated by sh RNA.Transfected with mi R-34a mimics reduced the survival of U87 cells in a dose-dependent manner.To more specifically establish the role of GJIC in mi R-34a induced growth inhibition of U87 cells,si RNA was used to knockdown the expression of Cx43,the dominant connexin expressed in U87 cells.CCK-8 assay showed that siR NAs have no effect on cell growth,but they could aggravate the growth inhibition of miR-34a to U87 cels.CONCLUSION Gap junctions enhance the antiproliferative effect of miR NA-34a in glioma cells.
基金supported by Jiangsu Provincial Special Programme of Medical Science(BL2014035) Changzhou Science and Technology Support Program(CE20155060+2 种基金CE20165048) Changzhou High-Level Medical Talents Training Project(2016CZBJ006) Changzhou Municipal Commissions o
文摘OBJECTIVE Glioblastoma multiforme(GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis.No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de.veloping new agents to treat GBM is important.This study aimed to evaluate the anti-tumor effect of evodiamine(Evo) on GBM cells,and to determine the underlying mechanisms involved.METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo.diamine(0-10 μmol·L^(-1)) for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS) production was detected using dichlorofluorescein diacetate(DCFH-DA) staining.The changes in mitochondrial mem.brane potential(MMP) were assessed by JC-1 after cells were treated with evodiamine.The expres.sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c,Caspase-3,cleaved Caspase-3,PRAP,and cleaved PARP were measured by Western blot analy.ses.RESULTS According to MTT assay results,Evo significantly inhibited the cell proliferation in a time-and dose-dependent manner.Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species(ROS) production and mitochondrial membrane potential(MMP) disruption.Finally,Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos.phorylation(p38 and JNK,but not ERK) to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas.pase-3,and PARP).CONCLUSION In summary,Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.
文摘Glioblastoma multiforme (GBM), the most commonprimary malignant brain tumor in adults is associated witha poor prognosis despite aggressive treatment withsurgical tumor debulking, radiation, and chemotherapy.Novel approaches including gene therapy provide newalternatives in the treatment of GBM. Apo-2 ligand(Apo-2L), a novel cytokine, is a member of the
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.
