白花蛇舌草治疗胶质瘤的实验研究及机制初探
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摘要
第一部分白花蛇舌草体外对人胶质瘤U87细胞增殖、凋亡和周期的影响
目的研究白花蛇舌草对胶质瘤U87细胞株的细胞增殖、凋亡和周期的影响。
方法用不同浓度的白花蛇舌草含药培养基(2、4、6、8mg/ml)处理U87细胞不同时间后,采用MTT法检测其对U87细胞增殖能力的影响,流式细胞仪检测对照组与实验组细胞的凋亡率差异,流式细胞术PI染色法检测细胞周期的改变。
结果经白花蛇舌草2、4、6、8mg/ml处理后,U87细胞增殖受到明显抑制,生存率显著降低,呈剂量依赖性；经白花蛇舌草(4、8mg/ml)处理后U87细胞的凋亡率分别增加到(17.31±1.36)%,(41.23±0.72)%,明显高于对照组的(8.11±1.71)%(P<0.01)；细胞周期分析结果显示,白花蛇舌草能改变细胞周期的分布,与空白对照组相比,白花蛇舌草4mg/ml组S期细胞与8mg/ml组G2/M期细胞百分比明显增加,两组细胞的G0/G1期百分比则呈剂量依赖性的下降趋势,差异有统计学意义(P<0.01)
结论：白花蛇舌草可诱导胶质瘤细胞凋亡和周期阻滞,使其增殖受抑,生存率降低。
第二部分白花蛇舌草体外抑制人胶质瘤U87细胞生长的机制初探
目的研究白花蛇舌草体外抑制胶质瘤U87细胞株的生长及其机制初探。
方法采用不同浓度的白花蛇舌草含药培养基(0、4、8mg/ml)处理U87细胞48h,免疫印迹法检测白花蛇舌草对U87细胞中抗凋亡基因(Bcl-2)和促凋亡基因(Bax)、半胱氨酸蛋白酶(Caspase-3)表达水平的影响。流式细胞仪检测实验组细胞的线粒体膜电位的改变.
结果白花蛇舌草能显著上调促凋亡基因Bax的表达并降低Bcl-2/Bax比率,促进U87细胞中Caspase-3的蛋白表达,且呈剂量依赖性。经JC-1染色法处理后,呈绿色荧光的U87细胞比率随含药培养基浓度升高而增多,分别为(11.90±0.20)%,(34.17±2.79)%,明显高于对照组的(5.53±1.20)%(P<0.05)。
讨论白花蛇舌草通过线粒体依赖性途径诱导人胶质瘤U87细胞的凋亡,从而抑制胶质瘤细胞的生长。
第三部分
白花蛇舌草体内对人脑胶质瘤U87细胞生长的影响
目的探讨对白花蛇舌草在体内对U87胶质瘤细胞的影响及其毒副作用。方法将U87胶质瘤肿瘤块移植于ICR小鼠皮下,制作小鼠胶质瘤动物模型,给予不同剂量的白花蛇舌草间质内注射。观察肿瘤的生长,计算并比较各组肿瘤的体积抑制率。观察药物处理后肿瘤HE染色变化。比较各组药物对小鼠的毒副作用。
结果治疗组的肿瘤体积抑制率分别为38%及42%,与对照组比较差异明显(P<0.05)。白花蛇舌草注射液组及白花蛇舌草注射液加生理盐水组起效较顺铂组慢,用药后21日有明显抑制肿瘤生长的作用,但较顺铂弱(P<0.05)。白花蛇舌草组肿瘤可见大片坏死,坏死边缘可见少量炎症细胞浸润,血管不同程度扩张充血。药物治疗后无明显的毒副作用。
结论：白花蛇舌草在体内有明显抑制肿瘤生长的作用,无明显毒副作用。
Part I
Effect of Hedyotic diffusa on apoptosis、proliferation and cell's cycle of U87glioma cells in vitro
Objective:To investigate the effect and the possible mechanism of apoptosis induction by hedyotic diffusa (HD) on human glioma U87cells.
Method:U87cells were cultured for24and72hours in medium which contained hedyotic diffusa with different concentrations, the methyl thiazolyl tetrazolium (MTT) assay was used to detect the survival rate, the apoptosis of the cells was examined by flow cytometry, the cell's cycle was examined by flow cytometry.
Results:The cells proliferation was obviously inhibited by hedyotic diffusa and showed a dose dependent manner. The apoptotic rates of the4and8mg/mlHD groups were17.31±1.36)%,41.23+0.72%respectively, all significantly higher than that of the0mg/ml HD group(P<0.05).The result of cell's cycle showed HD could effect the U87cell's cycle distribution。 When compared w ith o ther groups, cells in stage of S increased in HD4mg/ml group and cells in stage of G2/M increased in HD8mg/ml, the rate of G0/G1 showed a dose-dependent decreased in these two group (P<0.05).
Conclusion:Hedytotic diffusa could induce glioma U87cells apoptosis.After analysis of result of cell's cycl, We considered that HD could cause phage arrest and induce the apoptosis of U87glioma cells.
Part II
The study on the mechanism of suppression effect of Hedyotic diffusa on human glioma cells growth in vitro
Objective:To investigate the possible mechanism of of suppression effect of Hedyotic diffusa on human glioma U87cells growth in vitro
Methods:U87cells were cultured for24hours in medium which contained hedyotic diffusa with different concentrations(0、4、8mg/ml),the apoptosis of the cells and collapse of mitochondrial membrane potential were examined by flow cytometry,the change of Bcl-2and Bax proteins levels were measured by immunoblot.
Results:The protein expression of caspase-3was increased dose-dependently.And the proteins expression of Bax was increased and Bcl-2-to-Bax ratio was reduced dose-dependently. The JC-1-green-bright rates of cells treated with4,8mg/ml HD were (11.90+0.20)%,(34.17+2.79)%respectively,significantly higher than untreated U87cells (P<0.05)
Conclusion Hedytotic diffusa induced glioma U87cells apoptosis via mitochondrion pathway, then suppress human glioma U87cells growth.
Part Ⅲ
Effect of Hedyotic diffusa on U87glioma cells growth in vitro
Objective To investigate the effect and the possible mechanism of hedyotic diffusa (HD) on human glioma U87cells.
Method U87human glioma was inoculated into ICR mice to establish a human glioma xenograft glioma model. The tumor were treated by intratmoral injection with oldenlandia diffusa in different dosages. The negative control group was given saline, growth of tumor was observed, volume inhibition rates were calcutated and compared among every group. Study the change of HE staining and compare the side effect among every group.
Results Volume inhibition rates of treated group were38%and42%respectively, there were significant difference between treated group and control group(P<0.05).HD injection group and HD injection add saline group took effect more slowly than cisplatin group, showed obvious suppression to tumor growth after treated with HD for21days. HE staining showed large necrosis area, inflammatory cell infiltration was found at the edge of necrosis, hemangiectasis and congestion varied to various degrees. There were no side effect after treated with HD.
Conclusion Hedytotic diffusa could inhibitgrowth of tumor and no side effect.
目的研究白花蛇舌草对胶质瘤U87细胞株的细胞增殖、凋亡和周期的影响。
方法用不同浓度的白花蛇舌草含药培养基(2、4、6、8mg/ml)处理U87细胞不同时间后,采用MTT法检测其对U87细胞增殖能力的影响,流式细胞仪检测对照组与实验组细胞的凋亡率差异,流式细胞术PI染色法检测细胞周期的改变。
结果经白花蛇舌草2、4、6、8mg/ml处理后,U87细胞增殖受到明显抑制,生存率显著降低,呈剂量依赖性；经白花蛇舌草(4、8mg/ml)处理后U87细胞的凋亡率分别增加到(17.31±1.36)%,(41.23±0.72)%,明显高于对照组的(8.11±1.71)%(P<0.01)；细胞周期分析结果显示,白花蛇舌草能改变细胞周期的分布,与空白对照组相比,白花蛇舌草4mg/ml组S期细胞与8mg/ml组G2/M期细胞百分比明显增加,两组细胞的G0/G1期百分比则呈剂量依赖性的下降趋势,差异有统计学意义(P<0.01)
结论：白花蛇舌草可诱导胶质瘤细胞凋亡和周期阻滞,使其增殖受抑,生存率降低。
第二部分白花蛇舌草体外抑制人胶质瘤U87细胞生长的机制初探
目的研究白花蛇舌草体外抑制胶质瘤U87细胞株的生长及其机制初探。
方法采用不同浓度的白花蛇舌草含药培养基(0、4、8mg/ml)处理U87细胞48h,免疫印迹法检测白花蛇舌草对U87细胞中抗凋亡基因(Bcl-2)和促凋亡基因(Bax)、半胱氨酸蛋白酶(Caspase-3)表达水平的影响。流式细胞仪检测实验组细胞的线粒体膜电位的改变.
结果白花蛇舌草能显著上调促凋亡基因Bax的表达并降低Bcl-2/Bax比率,促进U87细胞中Caspase-3的蛋白表达,且呈剂量依赖性。经JC-1染色法处理后,呈绿色荧光的U87细胞比率随含药培养基浓度升高而增多,分别为(11.90±0.20)%,(34.17±2.79)%,明显高于对照组的(5.53±1.20)%(P<0.05)。
讨论白花蛇舌草通过线粒体依赖性途径诱导人胶质瘤U87细胞的凋亡,从而抑制胶质瘤细胞的生长。
第三部分
白花蛇舌草体内对人脑胶质瘤U87细胞生长的影响
目的探讨对白花蛇舌草在体内对U87胶质瘤细胞的影响及其毒副作用。方法将U87胶质瘤肿瘤块移植于ICR小鼠皮下,制作小鼠胶质瘤动物模型,给予不同剂量的白花蛇舌草间质内注射。观察肿瘤的生长,计算并比较各组肿瘤的体积抑制率。观察药物处理后肿瘤HE染色变化。比较各组药物对小鼠的毒副作用。
结果治疗组的肿瘤体积抑制率分别为38%及42%,与对照组比较差异明显(P<0.05)。白花蛇舌草注射液组及白花蛇舌草注射液加生理盐水组起效较顺铂组慢,用药后21日有明显抑制肿瘤生长的作用,但较顺铂弱(P<0.05)。白花蛇舌草组肿瘤可见大片坏死,坏死边缘可见少量炎症细胞浸润,血管不同程度扩张充血。药物治疗后无明显的毒副作用。
结论：白花蛇舌草在体内有明显抑制肿瘤生长的作用,无明显毒副作用。
Part I
Effect of Hedyotic diffusa on apoptosis、proliferation and cell's cycle of U87glioma cells in vitro
Objective:To investigate the effect and the possible mechanism of apoptosis induction by hedyotic diffusa (HD) on human glioma U87cells.
Method:U87cells were cultured for24and72hours in medium which contained hedyotic diffusa with different concentrations, the methyl thiazolyl tetrazolium (MTT) assay was used to detect the survival rate, the apoptosis of the cells was examined by flow cytometry, the cell's cycle was examined by flow cytometry.
Results:The cells proliferation was obviously inhibited by hedyotic diffusa and showed a dose dependent manner. The apoptotic rates of the4and8mg/mlHD groups were17.31±1.36)%,41.23+0.72%respectively, all significantly higher than that of the0mg/ml HD group(P<0.05).The result of cell's cycle showed HD could effect the U87cell's cycle distribution。 When compared w ith o ther groups, cells in stage of S increased in HD4mg/ml group and cells in stage of G2/M increased in HD8mg/ml, the rate of G0/G1 showed a dose-dependent decreased in these two group (P<0.05).
Conclusion:Hedytotic diffusa could induce glioma U87cells apoptosis.After analysis of result of cell's cycl, We considered that HD could cause phage arrest and induce the apoptosis of U87glioma cells.
Part II
The study on the mechanism of suppression effect of Hedyotic diffusa on human glioma cells growth in vitro
Objective:To investigate the possible mechanism of of suppression effect of Hedyotic diffusa on human glioma U87cells growth in vitro
Methods:U87cells were cultured for24hours in medium which contained hedyotic diffusa with different concentrations(0、4、8mg/ml),the apoptosis of the cells and collapse of mitochondrial membrane potential were examined by flow cytometry,the change of Bcl-2and Bax proteins levels were measured by immunoblot.
Results:The protein expression of caspase-3was increased dose-dependently.And the proteins expression of Bax was increased and Bcl-2-to-Bax ratio was reduced dose-dependently. The JC-1-green-bright rates of cells treated with4,8mg/ml HD were (11.90+0.20)%,(34.17+2.79)%respectively,significantly higher than untreated U87cells (P<0.05)
Conclusion Hedytotic diffusa induced glioma U87cells apoptosis via mitochondrion pathway, then suppress human glioma U87cells growth.
Part Ⅲ
Effect of Hedyotic diffusa on U87glioma cells growth in vitro
Objective To investigate the effect and the possible mechanism of hedyotic diffusa (HD) on human glioma U87cells.
Method U87human glioma was inoculated into ICR mice to establish a human glioma xenograft glioma model. The tumor were treated by intratmoral injection with oldenlandia diffusa in different dosages. The negative control group was given saline, growth of tumor was observed, volume inhibition rates were calcutated and compared among every group. Study the change of HE staining and compare the side effect among every group.
Results Volume inhibition rates of treated group were38%and42%respectively, there were significant difference between treated group and control group(P<0.05).HD injection group and HD injection add saline group took effect more slowly than cisplatin group, showed obvious suppression to tumor growth after treated with HD for21days. HE staining showed large necrosis area, inflammatory cell infiltration was found at the edge of necrosis, hemangiectasis and congestion varied to various degrees. There were no side effect after treated with HD.
Conclusion Hedytotic diffusa could inhibitgrowth of tumor and no side effect.
引文
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