AIM: The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS: The effect of AFP on the...AIM: The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS: The effect of AFP on the proliferation of NIH 3T3 cells was measured by incorporation of 3H-TdR. Receptor-binding assay of 125I-AFP was performed to detect the properties of AFP receptor in NIH 3T3 cells. The influences of AFP on the [cAMP]i and the activities of protein kinase A (PKA) were determined. Western blot was used to detect the change of K-ras P21 protein expression. RESULTS: The proliferation of NIH 3T3 cells treated with 0-80 mg/L of AFP was significantly enhanced. The Scatchard analysis indicated that there were two classes of binding sites with KD of 2.722 x 10(-9)M (Bmax=12810 sites per cell) and 8.931 x 10(-8)M (Bmax=119700 sites per cell) respectively. In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L. The monoclonal antibody against AFP could reverse the effects of AFP on the cAMP content, PKA activity and the expression of K-ras p21 gene. CONCLUSION: The effect of AFP on the cell proliferation was achieved by binding its receptor to trigger the signal transduction pathway of cAMP-PKA and alter the expression of K- ras p21 gene.展开更多
To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we establishe...To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8- and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H2O2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H2O2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.展开更多
Multidrug resistance （MDR） is a major problem in cancer chemotherapy. One of the best known mechanisms of MDR is the elevated expression of ATP-binding cassette （ABC） transporters. While some members of human ABC ...Multidrug resistance （MDR） is a major problem in cancer chemotherapy. One of the best known mechanisms of MDR is the elevated expression of ATP-binding cassette （ABC） transporters. While some members of human ABC transporters have been shown to cause drug resistance with elevated expression, it is not yet known whether the over-expression of other members could also contribute to drug resistance in many model cancer cell lines and clinics. The recent development ofmicroarrays and quantitative PCR arrays for expression profiling analysis of ABC transporters has helped address these issues. In this article, various arrays with limited or full list of ABC transporter genes and their use in identifying ABC transporter genes in drug resistance and chemo-sensitivity prediction will be reviewed.展开更多
目的探讨盐酸表柔比星联合铂类对晚期耐药性子宫内膜癌患者生存时间及生活质量的影响,为临床治疗提供参考。方法回顾性分析2013年7月至2015年6月在山东省青岛市市立医院接受治疗的晚期子宫内膜癌患者100例,根据治疗方法不同分为观察组(5...目的探讨盐酸表柔比星联合铂类对晚期耐药性子宫内膜癌患者生存时间及生活质量的影响,为临床治疗提供参考。方法回顾性分析2013年7月至2015年6月在山东省青岛市市立医院接受治疗的晚期子宫内膜癌患者100例,根据治疗方法不同分为观察组(50例)和对照组(50例)。对照组患者给予顺铂治疗,观察组患者给予盐酸表柔比星联合顺铂治疗。比较两组患者治疗后的临床效果与生活质量,记录两组患者治疗前后血清卵巢癌抗原(ovarian cancer antigen,CA125)、脂联素(adiponectin,APN)水平的变化,1年、2年、3年生存率,以及治疗期间患者骨髓抑制、血小板下降、恶心等不良反应的发生率。结果观察组患者治疗总有效率为86.00%,高于对照组的68.00%,差异有显著性(P<0.05)。治疗后,观察组患者自觉症状、心理情绪状态、日常生活、社会活动、生活质量评分均高于对照组(P<0.05)。与治疗前比较,两组患者治疗后CA125表达水平均明显降低,且观察组明显低于对照组,APN表达水平均明显升高,且观察组明显高于对照组,差异均有显著性(P<0.05)。观察组患者1年、2年、3年生存率均高于对照组(P<0.05)。治疗期间,两组患者均有出现骨髓抑制、血小板下降、恶心等不良反应,观察组发生率为8.00%,明显低于对照组的24.00%,差异有显著性(P<0.05)。结论盐酸表柔比星联合铂类治疗晚期耐药性子宫内膜癌效果显著,可调节血清CA125、APN的表达,提高患者的生活质量以及生存率,安全性高,值得临床推广使用。展开更多
基金This work was supported by National NaturalScience Fundation of China(No.39760077).
文摘AIM: The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS: The effect of AFP on the proliferation of NIH 3T3 cells was measured by incorporation of 3H-TdR. Receptor-binding assay of 125I-AFP was performed to detect the properties of AFP receptor in NIH 3T3 cells. The influences of AFP on the [cAMP]i and the activities of protein kinase A (PKA) were determined. Western blot was used to detect the change of K-ras P21 protein expression. RESULTS: The proliferation of NIH 3T3 cells treated with 0-80 mg/L of AFP was significantly enhanced. The Scatchard analysis indicated that there were two classes of binding sites with KD of 2.722 x 10(-9)M (Bmax=12810 sites per cell) and 8.931 x 10(-8)M (Bmax=119700 sites per cell) respectively. In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L. The monoclonal antibody against AFP could reverse the effects of AFP on the cAMP content, PKA activity and the expression of K-ras p21 gene. CONCLUSION: The effect of AFP on the cell proliferation was achieved by binding its receptor to trigger the signal transduction pathway of cAMP-PKA and alter the expression of K- ras p21 gene.
基金This work was kindly supported by Na-tional Natural Science Foundation of China(No.39670308)
文摘To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8- and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H2O2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H2O2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.
文摘Multidrug resistance （MDR） is a major problem in cancer chemotherapy. One of the best known mechanisms of MDR is the elevated expression of ATP-binding cassette （ABC） transporters. While some members of human ABC transporters have been shown to cause drug resistance with elevated expression, it is not yet known whether the over-expression of other members could also contribute to drug resistance in many model cancer cell lines and clinics. The recent development ofmicroarrays and quantitative PCR arrays for expression profiling analysis of ABC transporters has helped address these issues. In this article, various arrays with limited or full list of ABC transporter genes and their use in identifying ABC transporter genes in drug resistance and chemo-sensitivity prediction will be reviewed.
文摘目的探讨盐酸表柔比星联合铂类对晚期耐药性子宫内膜癌患者生存时间及生活质量的影响,为临床治疗提供参考。方法回顾性分析2013年7月至2015年6月在山东省青岛市市立医院接受治疗的晚期子宫内膜癌患者100例,根据治疗方法不同分为观察组(50例)和对照组(50例)。对照组患者给予顺铂治疗,观察组患者给予盐酸表柔比星联合顺铂治疗。比较两组患者治疗后的临床效果与生活质量,记录两组患者治疗前后血清卵巢癌抗原(ovarian cancer antigen,CA125)、脂联素(adiponectin,APN)水平的变化,1年、2年、3年生存率,以及治疗期间患者骨髓抑制、血小板下降、恶心等不良反应的发生率。结果观察组患者治疗总有效率为86.00%,高于对照组的68.00%,差异有显著性(P<0.05)。治疗后,观察组患者自觉症状、心理情绪状态、日常生活、社会活动、生活质量评分均高于对照组(P<0.05)。与治疗前比较,两组患者治疗后CA125表达水平均明显降低,且观察组明显低于对照组,APN表达水平均明显升高,且观察组明显高于对照组,差异均有显著性(P<0.05)。观察组患者1年、2年、3年生存率均高于对照组(P<0.05)。治疗期间,两组患者均有出现骨髓抑制、血小板下降、恶心等不良反应,观察组发生率为8.00%,明显低于对照组的24.00%,差异有显著性(P<0.05)。结论盐酸表柔比星联合铂类治疗晚期耐药性子宫内膜癌效果显著,可调节血清CA125、APN的表达,提高患者的生活质量以及生存率,安全性高,值得临床推广使用。
