OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like g...OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.展开更多
基金supported by National Natural Science Foundation of China(81502123 and81330081)Natural Science Foundation of Anhui Province(1308085QH130)Anhui Province Nature Science Foundation in University(KJ2014A119)
文摘OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.
文摘目的探讨急性脑梗死(acute cerebral infarction,ACI)患者脑电图、血清胰岛素生长因子1(insulin-like growth factor 1,IGF-1)、神经元特异性烯醇化酶(neuron-specific enolase,NSE)与病灶体积及美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分的关系。方法选择2021年8月至2022年12月在南京市溧水区人民医院神经内科首次确诊的ACI患者218例,根据病灶体积分为大体积组63例、中体积组103例和小体积组52例。检测患者脑电图(δ+θ)与(α+β)功率比[(δ+θ)/(α+β)ratio,DTABR]、大脑对称指数(brainspine interface,BSI)、血清IGF-1和NSE水平,观察上述指标与MRI检查脑梗死病灶体积、NIHSS评分、阿替普酶溶栓后2周、4周时NIHSS评分的相关性。结果中体积组和大体积组IGF-1水平明显低于小体积组,NSE、DTABR、BSI明显高于小体积组(P<0.05);大体积组IGF-1水平明显低于中体积组,NSE、DTABR、BSI明显高于中体积组(P<0.05)。DTABR、BSI、血清NSE与病灶体积(r=0.563,P=0.000;r=0.318,P=0.038;r=0.673,P=0.000)和治疗前NIHSS评分(r=0.499,P=0.000;r=0.362,P=0.013;r=0.750,P=0.001)呈显著正相关。血清IGF-1水平与病灶体积(r=-0.572,P=0.000)和治疗前NIHSS评分(r=-0.438,P=0.001)呈显著负相关。DTABR、BSI、血清NSE、病灶体积均与溶栓后2、4周NIHSS评分呈正相关,IGF-1与溶栓后2、4周NIHSS评分呈负相关(P<0.05,P<0.01)。结论ACI患者脑电图、IGF-1和NSE与病灶体积和溶栓后NIHSS评分显著相关。
