曲古菌素A抑制人结肠癌HCT-116细胞株生长及其机制的实验研究
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摘要
目的:探讨曲古菌素A(trichostatin A ,TSA)对人结肠癌细胞株HCT-116生长的影响及可能的作用机制。
方法:(1)将TSA作用于结肠癌细胞系HCT-116细胞,CCK8法检测吸光度值,计算对照组和各实验组细胞的生长抑制率。(2)应用流式细胞仪(FCM)研究TSA对人结肠癌HCT-116细胞周期和凋亡的影响;(3)Western Blot检测DMTF1、CyclinD1、Bid、乙酰化H3的蛋白表达水平变化。
结果:(1)CCK8法显示各浓度(75ng/ml、150ng/ml、300ng/ml、600ng/ml)组TSA均可抑制HCT-116细胞的生长,实验组与对照组及各实验组之间差别均有统计学意义(P<0.05),并呈时间和剂量依赖性。(2)流式细胞仪检测发现HCT-116细胞经TSA作用48小时后可见细胞周期S期明显抑制,且随着浓度的增加HCT-116细胞周期G0/G1期比例增加,S期细胞比例下降,具有统计学意义(P<0.05)。不同浓度的TSA(75ng/ml、150ng/ml、300ng/ml、600ng/ml)作用结肠癌HCT-116细胞48h后,凋亡率分别为(4.6±0.55)%、(37.06±7.89)%、(71.2±5.55)%、(75.93±3.28)%,各TSA组细胞凋亡率均明显高于对照组(P<0.05)。(3)Western Blot显示不同浓度TSA作用于结肠癌HCT-116细胞48h后,细胞中的DMTF1、Bid、乙酰化H3蛋白表达上调,而CyclinD1表达下降。
结论:(1)TSA能明显抑制体外培养的人结肠癌HCT-116细胞生长,并呈时间和剂量依赖性;(2)TSA能诱导细胞凋亡并使细胞周期阻滞于G0/G1期;(3)TSA对结肠癌HCT-116细胞生长的抑制作用可能与阻滞细胞周期、诱导凋亡、下调CyclinD1表达和上调DMTF1、Bid、乙酰化H3表达有关。
Objective:To Study the Anti-Tumor Effect and its Mechanisms of trichostatin A on Human Colon Cancer HCT-116 Cell Line In Vitro.
Methods: In vitro,human colon cancer cell line HCT-116 were treated with trichostatin A by means of CCK8 assay,the absorbance value was detected and growth inhibition rate was calculated.Cell cycle and apoptosis was assessed by flow cytometry,Western Blot was taken to detect DMTF1、CyclinD1、Bid and acetylated histone3 protein expression.
Results:CCK8 assay indicated that the inhibitory effect of different concentrion (75ng/ml,150ng/ml,300ng/ml,600ng/ml)trichostatin A on the proliferation of HCT-116 cell was found in dose-and-time dependent manner.There was great statistical signification between varies medicated group and control group(P<0.05),and there also were great statistical signification between medicated group each other(P<0.05).Flow cytometry showed that the HCT-116 cell cycle was induced by trichostatin A at 48 hours,the ratio of G0/G1 phase was increased and the ratio of S phase was decreased significantly (P<0.05). meanwhile, The proportion of apoptosis of trichostatin A (75、150、300、600ng/ml) group in the 48h was(4.6±0.55)%、(37.06±7.89)%、(71.2±5.55)%、(75.93±3.28)%,respectively, which were all significantly higher than the blank control group(P<0.05). Western blotting indicated that trichostatin A can down- regulate the expression of CylinD1,up-regulate the expression of DMTF1、bid and acetylated histone3 in cell.
Conclusion: Arichostatin A could inhibit the growth of HCT-116 cell in dose-and-time dependent maner. It could also induce HCT-116 cell apoptosis and arrest cell cycle at the phase of G0/G1.TSA on the HCT-116 colon cancer cell growth inhibition may block the cell cycle,inducing apoptosis and down-regulate the expression of CylinD1,up-regulate the expression of DMTF1,Bid and acetylated histone3 and so on.
方法:(1)将TSA作用于结肠癌细胞系HCT-116细胞,CCK8法检测吸光度值,计算对照组和各实验组细胞的生长抑制率。(2)应用流式细胞仪(FCM)研究TSA对人结肠癌HCT-116细胞周期和凋亡的影响;(3)Western Blot检测DMTF1、CyclinD1、Bid、乙酰化H3的蛋白表达水平变化。
结果:(1)CCK8法显示各浓度(75ng/ml、150ng/ml、300ng/ml、600ng/ml)组TSA均可抑制HCT-116细胞的生长,实验组与对照组及各实验组之间差别均有统计学意义(P<0.05),并呈时间和剂量依赖性。(2)流式细胞仪检测发现HCT-116细胞经TSA作用48小时后可见细胞周期S期明显抑制,且随着浓度的增加HCT-116细胞周期G0/G1期比例增加,S期细胞比例下降,具有统计学意义(P<0.05)。不同浓度的TSA(75ng/ml、150ng/ml、300ng/ml、600ng/ml)作用结肠癌HCT-116细胞48h后,凋亡率分别为(4.6±0.55)%、(37.06±7.89)%、(71.2±5.55)%、(75.93±3.28)%,各TSA组细胞凋亡率均明显高于对照组(P<0.05)。(3)Western Blot显示不同浓度TSA作用于结肠癌HCT-116细胞48h后,细胞中的DMTF1、Bid、乙酰化H3蛋白表达上调,而CyclinD1表达下降。
结论:(1)TSA能明显抑制体外培养的人结肠癌HCT-116细胞生长,并呈时间和剂量依赖性;(2)TSA能诱导细胞凋亡并使细胞周期阻滞于G0/G1期;(3)TSA对结肠癌HCT-116细胞生长的抑制作用可能与阻滞细胞周期、诱导凋亡、下调CyclinD1表达和上调DMTF1、Bid、乙酰化H3表达有关。
Objective:To Study the Anti-Tumor Effect and its Mechanisms of trichostatin A on Human Colon Cancer HCT-116 Cell Line In Vitro.
Methods: In vitro,human colon cancer cell line HCT-116 were treated with trichostatin A by means of CCK8 assay,the absorbance value was detected and growth inhibition rate was calculated.Cell cycle and apoptosis was assessed by flow cytometry,Western Blot was taken to detect DMTF1、CyclinD1、Bid and acetylated histone3 protein expression.
Results:CCK8 assay indicated that the inhibitory effect of different concentrion (75ng/ml,150ng/ml,300ng/ml,600ng/ml)trichostatin A on the proliferation of HCT-116 cell was found in dose-and-time dependent manner.There was great statistical signification between varies medicated group and control group(P<0.05),and there also were great statistical signification between medicated group each other(P<0.05).Flow cytometry showed that the HCT-116 cell cycle was induced by trichostatin A at 48 hours,the ratio of G0/G1 phase was increased and the ratio of S phase was decreased significantly (P<0.05). meanwhile, The proportion of apoptosis of trichostatin A (75、150、300、600ng/ml) group in the 48h was(4.6±0.55)%、(37.06±7.89)%、(71.2±5.55)%、(75.93±3.28)%,respectively, which were all significantly higher than the blank control group(P<0.05). Western blotting indicated that trichostatin A can down- regulate the expression of CylinD1,up-regulate the expression of DMTF1、bid and acetylated histone3 in cell.
Conclusion: Arichostatin A could inhibit the growth of HCT-116 cell in dose-and-time dependent maner. It could also induce HCT-116 cell apoptosis and arrest cell cycle at the phase of G0/G1.TSA on the HCT-116 colon cancer cell growth inhibition may block the cell cycle,inducing apoptosis and down-regulate the expression of CylinD1,up-regulate the expression of DMTF1,Bid and acetylated histone3 and so on.
引文
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