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车佳.白藜芦醇通过下调HAX-1的表达提高耐药结直肠癌细胞对TRAIL的敏感性[J].浙江中西医结合杂志,2017,27(11):
白藜芦醇通过下调HAX-1的表达提高耐药结直肠癌细胞对TRAIL的敏感性
Resveratrol increased the sensitivity of drug-resistant colorectal cancer cells to TRAIL through downregulating the expression of HAX-1
投稿时间:2017-05-17  修订日期:2017-05-22
DOI:
中文关键词:  白藜芦醇  TRAIL  结直肠癌  HAX-1  凋亡
英文关键词:Resveratrol  TRAIL  colorectal cancer  HAX-1  apoptosis
基金项目:
作者单位E-mail
车佳* 浙江省立同德医院 tongdechejia@sina.com 
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中文摘要:
      目的: 探讨天然药物白藜芦醇是否能提高耐药结直肠癌细胞对TRAIL的敏感性并研究其机制。方法: 将TRAIL耐药HT29细胞(TR-HT29细胞)按对照组,白藜芦醇组,TRAIL组,白藜芦醇+TRAIL组及白藜芦醇+TRAIL+HAX-1质粒组进行分组后,CCK-8法检测TR-HT29的细胞活力,流式细胞术检测TR-HT29细胞的凋亡程度和线粒体膜电位,western blot实验检测TR-HT29细胞HAX-1的表达水平、细胞色素c的释放和caspase-3的活化。结果: TR-HT29细胞对TRAIL的半数有效浓度(IC50)(19.4±1.3 ng/ml)显著高于HT29细胞(1.8±0.2, P<0.05)。白藜芦醇处理可显著抑制TR-HT29细胞中HAX-1蛋白的表达水平。白藜芦醇+TRAIL组TR-HT29的细胞活力抑制率(53.6±4.4 %)和凋亡诱导率(39.4±2.9 %)显著高于TRAIL组的细胞活力抑制率(14.3±1.0 %, P<0.05)、凋亡诱导率(9.6±0.7 %, P<0.05)和白藜芦醇+TRAIL+HAX-1质粒组的细胞活力抑制率(19.9±1.5 %, P<0.05)、凋亡诱导率(13.8±1.1 %, P<0.05)。白藜芦醇+TRAIL组TR-HT29的线粒体膜电位显著低于TRAIL组和白藜芦醇+TRAIL+HAX-1质粒组。白藜芦醇+TRAIL组TR-HT29细胞色素c的释放和caspase-3的活化显著高于TRAIL组和白藜芦醇+TRAIL+HAX-1质粒组。结论: 白藜芦醇通过下调HAX-1的表达提高耐药结直肠癌细胞对TRAIL的敏感性。
英文摘要:
      AIM: To investigate the effect and mechanism of resveratrol on increasing the sensitivity of drug-resistant colorectal cancer cells to TRAIL treatment. Methods: TRAIL-resistant HT29 (TR-HT29) cells were divided into control group, resveratrol group, TRAIL group, resveratrol + TRAIL group and resveratrol + TRAIL + HAX-1 plasmid group. CCK-8 assays were performed to evaluate the cell viability of TR-HT29 cells, Flow cytometry analysis was performed to detect the cell apoptosis and mitochondrial membrane potential. Western blot analysis was performed to detect the release of cytochrome c and activation of caspase-3. Results: IC50 of TRAIL to TR-HT29 (19.4±1.3 ng/ml) was significantly higher than the HT29 cells (1.8±0.2, P<0.05). Resveratrol treatment was able to suppress the expression of HAX-1 in TR-HT29 cells. Inhibitory rate of cell viability (53.6±4.4 %) and apoptotic rate (39.4±2.9 %) in TRAIL + resveratrol group was significantly higher than the inhibitory rate of cell viability (14.3±1.0 %, P<0.05) and apoptotic rate (9.6±0.7 %, P<0.05) in TRAIL group and inhibitory rate of cell viability (19.9±1.5 %, P<0.05) and apoptotic rate (13.8±1.1 %, P<0.05) in TRAIL + resveratrol + HAX-1 plasmid group. Mitochondrial membrane potential of TR-HT29 in TRAIL + resveratrol group was significantly higher than that in the TRAIL group and TRAIL + resveratrol + HAX-1 plasmid group. Release of cytochrome c and activation of caspase-3 in TRAIL + resveratrol group was significantly higher than that in the TRAIL group and TRAIL + resveratrol + HAX-1 plasmid group. Conclusion: Resveratrol increased the sensitivity of drug-resistant colorectal cancer cells to TRAIL through downregulating the expression of HAX-1.
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