Tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） is a promising anti-cancer agent. Epigallocatechin-3-gallate （EGCG） is a polyphenolic constituent of green tea. In this study, inhibitory effect of c...Tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） is a promising anti-cancer agent. Epigallocatechin-3-gallate （EGCG） is a polyphenolic constituent of green tea. In this study, inhibitory effect of combined use of EGCG and TRAIL on human melanoma A375 cells was examined and the possible mechanism investigated. The cells were divided into 4 groups： control group, EGCG group （EGCG： 10, 20 μg/mL）, TRAIL group （TRAIL： 25 ng/mL） and EGCG＋TRAIL group （combined group）. The growth inhibition was measured in the A375 cells treated with different concentrations of TRAIL （（25, 50, 75, 100, 125, 150 ng/mL） by MTT assay. The apoptosis was assessed by flow cytometry. The expressions of DR4 and DR5 were detected by flow cytometry and western blotting. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that TRAIL could dose-dependently inhibit the growth of A375 cells and the IC50 of TRAIL was 150 ng/mL. The apoptosis rate was 11.8% in the TRAIL group, 5%–7% in the EGCG group and 48.9%–59.1% in the combined group. Significant difference was found in the apoptosis rate between the combined group and the EGCG or TRAIL group （P〈0.05 for each）. The expression of DR4 instead of DR5 was significantly increased in the EGCG group. The activity of caspase-3 rather than caspase-8 was substantially enhanced in the EGCG group. These results suggest that EGCG is useful for the TRAIL-based treatment for melanoma.展开更多
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. However, emergence of drug resistance limits its potential use. Plumbagin is a natural quinonoid compound isolated from...Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. However, emergence of drug resistance limits its potential use. Plumbagin is a natural quinonoid compound isolated from plant. In this study, induced apoptosis effect of the combined treatment with plumbagin and TRAIL on human melanoma A375 cell line was examined and possible mechanism was investigated. The cells were divided into four groups: control group, plumbagin group (plumbagin, 5 or 10 μmol/L), TRAIL group (TRAIL, 30 ng/mL) and plumbagin+TRAIL group (combined treatment group). The apoptosis, and the expression of DR4 and DR5 were detected by flow cytometry. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that the apoptosis rate was 8.3% in TRAIL group, 10.35%–16.94% in plumbagin group and 52.39%–65.39% in combined treatment group, respectively, with the difference being significant between combined treatment group and plumbagin or TRAIL group (P<0.05 for each). Moreover, plumbagin alone could markedly up-regulate DR5 mRNA and protein expression, and slightly increase DR4 mRNA and protein expression. Treatment of human melanoma A375 cells with plumbagin resulted in the activation of Caspase-3, but not Caspase-8. These results suggest that plumbagin might be useful for TRAIL-based treatment for melanoma.展开更多
目的探讨血液灌流联合甲泼尼龙、他克莫司和/或环磷酰胺等治疗抗黑色素瘤分化相关基因-5(melanoma differentiation-associated gene 5,MDA5)抗体阳性皮肌炎合并快速进展性间质性肺病的疗效和安全性。方法回顾性分析2016年3月~2018年11...目的探讨血液灌流联合甲泼尼龙、他克莫司和/或环磷酰胺等治疗抗黑色素瘤分化相关基因-5(melanoma differentiation-associated gene 5,MDA5)抗体阳性皮肌炎合并快速进展性间质性肺病的疗效和安全性。方法回顾性分析2016年3月~2018年11月在河北医科大学附属石家庄平安医院治疗的抗MDA5阳性皮肌炎合并快速进展性间质性肺病12例患者,均使用HA280树脂灌流器进行血液灌流治疗,同时联合应用甲泼尼龙、他克莫司和/或环磷酰胺等药物。收集患者治疗前后外周血淋巴细胞计数、白介素(interleukin,IL)-6、IL-10、C反应蛋白、肺泡Ⅱ型细胞表面抗原-6(Krebs Von den Lungen-6,KL-6)、铁蛋白、动脉血氧分压、动脉血二氧化碳分压、肺部高分辨CT评分等指标。治疗前、治疗后2周及4周间比较采用方差分析,两两比较采用LSD-t检验。结果2例死亡,其余10例患者随访至今存活。经过4周治疗与治疗前对比,血清IL-6、IL-10、KL-6、铁蛋白、C反应蛋白明显下降(F值分别为6.593,9.029,7.872,8.760,20.490;P值分别为0.005,0.001,0.002,0.001,<0.001),外周血淋巴细胞计数、动脉血氧分压、动脉血二氧化碳分压明显改善(F值分别为16.810,3.580,3.467;P值分别为<0.001,0.042,0.046),肺部高分辨CT评分改善(F=2.073,P=0.145),但无统计学意义。结论血液灌流联合甲泼尼龙、他克莫司和/或环磷酰胺等治疗抗MDA5抗体阳性皮肌炎合并快速进展性间质性肺病具有较好疗效,且安全性较好。展开更多
文摘Tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） is a promising anti-cancer agent. Epigallocatechin-3-gallate （EGCG） is a polyphenolic constituent of green tea. In this study, inhibitory effect of combined use of EGCG and TRAIL on human melanoma A375 cells was examined and the possible mechanism investigated. The cells were divided into 4 groups： control group, EGCG group （EGCG： 10, 20 μg/mL）, TRAIL group （TRAIL： 25 ng/mL） and EGCG＋TRAIL group （combined group）. The growth inhibition was measured in the A375 cells treated with different concentrations of TRAIL （（25, 50, 75, 100, 125, 150 ng/mL） by MTT assay. The apoptosis was assessed by flow cytometry. The expressions of DR4 and DR5 were detected by flow cytometry and western blotting. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that TRAIL could dose-dependently inhibit the growth of A375 cells and the IC50 of TRAIL was 150 ng/mL. The apoptosis rate was 11.8% in the TRAIL group, 5%–7% in the EGCG group and 48.9%–59.1% in the combined group. Significant difference was found in the apoptosis rate between the combined group and the EGCG or TRAIL group （P〈0.05 for each）. The expression of DR4 instead of DR5 was significantly increased in the EGCG group. The activity of caspase-3 rather than caspase-8 was substantially enhanced in the EGCG group. These results suggest that EGCG is useful for the TRAIL-based treatment for melanoma.
基金supported by a grant from National Natural Sciences Foundation of China (No.30972654/H1103)
文摘Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. However, emergence of drug resistance limits its potential use. Plumbagin is a natural quinonoid compound isolated from plant. In this study, induced apoptosis effect of the combined treatment with plumbagin and TRAIL on human melanoma A375 cell line was examined and possible mechanism was investigated. The cells were divided into four groups: control group, plumbagin group (plumbagin, 5 or 10 μmol/L), TRAIL group (TRAIL, 30 ng/mL) and plumbagin+TRAIL group (combined treatment group). The apoptosis, and the expression of DR4 and DR5 were detected by flow cytometry. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that the apoptosis rate was 8.3% in TRAIL group, 10.35%–16.94% in plumbagin group and 52.39%–65.39% in combined treatment group, respectively, with the difference being significant between combined treatment group and plumbagin or TRAIL group (P<0.05 for each). Moreover, plumbagin alone could markedly up-regulate DR5 mRNA and protein expression, and slightly increase DR4 mRNA and protein expression. Treatment of human melanoma A375 cells with plumbagin resulted in the activation of Caspase-3, but not Caspase-8. These results suggest that plumbagin might be useful for TRAIL-based treatment for melanoma.
文摘目的探讨血液灌流联合甲泼尼龙、他克莫司和/或环磷酰胺等治疗抗黑色素瘤分化相关基因-5(melanoma differentiation-associated gene 5,MDA5)抗体阳性皮肌炎合并快速进展性间质性肺病的疗效和安全性。方法回顾性分析2016年3月~2018年11月在河北医科大学附属石家庄平安医院治疗的抗MDA5阳性皮肌炎合并快速进展性间质性肺病12例患者,均使用HA280树脂灌流器进行血液灌流治疗,同时联合应用甲泼尼龙、他克莫司和/或环磷酰胺等药物。收集患者治疗前后外周血淋巴细胞计数、白介素(interleukin,IL)-6、IL-10、C反应蛋白、肺泡Ⅱ型细胞表面抗原-6(Krebs Von den Lungen-6,KL-6)、铁蛋白、动脉血氧分压、动脉血二氧化碳分压、肺部高分辨CT评分等指标。治疗前、治疗后2周及4周间比较采用方差分析,两两比较采用LSD-t检验。结果2例死亡,其余10例患者随访至今存活。经过4周治疗与治疗前对比,血清IL-6、IL-10、KL-6、铁蛋白、C反应蛋白明显下降(F值分别为6.593,9.029,7.872,8.760,20.490;P值分别为0.005,0.001,0.002,0.001,<0.001),外周血淋巴细胞计数、动脉血氧分压、动脉血二氧化碳分压明显改善(F值分别为16.810,3.580,3.467;P值分别为<0.001,0.042,0.046),肺部高分辨CT评分改善(F=2.073,P=0.145),但无统计学意义。结论血液灌流联合甲泼尼龙、他克莫司和/或环磷酰胺等治疗抗MDA5抗体阳性皮肌炎合并快速进展性间质性肺病具有较好疗效,且安全性较好。
