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宣丽杨.桔梗皂苷D通过下调HAX1的表达抑制肝癌干细胞对5-氟尿嘧啶的抵抗性[J].浙江中西医结合杂志,2017,27(9):
桔梗皂苷D通过下调HAX1的表达抑制肝癌干细胞对5-氟尿嘧啶的抵抗性
Platycodin D inhibits the resistance of liver cancer stem cells to 5-fluorouracil via down-regulating the expression of HAX1
投稿时间:2017-02-05  修订日期:2017-05-12
DOI:
中文关键词:  桔梗皂苷D  5-氟尿嘧啶  肝癌干细胞  HAX1  线粒体  凋亡
英文关键词:platycodin D  5-fluorouracil  liver cancer stem cells  HAX1  mitochondria  apoptosis
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作者单位E-mail
宣丽杨 浙江省立同德医院 tongdexuanliyang@163.com 
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中文摘要:
      目的: 探讨天然药物活性成分桔梗皂苷D是否能抑制肝癌干细胞对5-氟尿嘧啶的抵抗性并研究其机制。方法: MTT法和Annexin V染色流式细胞术检测桔梗皂苷D和5-氟尿嘧啶对HepG2肿瘤干细胞细胞活力和细胞凋亡的影响。采用western blot方法检测桔梗皂苷D是否调节HepG2肿瘤干细胞中HAX1的表达。运用JC-1染色流式细胞术、Annexin V染色流式细胞术及western blot方法研究桔梗皂苷D联合5-氟尿嘧啶对肝癌干细胞凋亡通路的影响。结果: 5 mmol/L 5-氟尿嘧啶处理下HepG2肿瘤干细胞的细胞活力抑制率为29.1±2.4,显著低于常规HepG2细胞的细胞活力抑制率(72.7±5.2, P<0.05)。5-氟尿嘧啶联合桔梗皂苷D对HepG2肿瘤干细胞的细胞活力的抑制率为66.7±3.4,凋亡诱导率为33.9±2.1,显著高于5-氟尿嘧啶单独处理的细胞活力抑制率(28.7±1.8,P<0.05)和凋亡诱导率(8.9±0.6,P<0.05)。桔梗皂苷D处理后HepG2肿瘤干细胞中HAX1的相对表达水平为0.24±0.02,相比于对照组(0.78±0.05)显著下降(P<0.05),表明桔梗皂苷D抑制肝癌干细胞HAX1的表达水平。5-氟尿嘧啶+桔梗皂苷D+HAX1质粒组的HepG2肿瘤干细胞凋亡率(10.1±0.7)显著低于5-氟尿嘧啶+桔梗皂苷D组(34.8±2.2,P<0.05),表明桔梗皂苷D通过下调HAX1的表达提高5-氟尿嘧啶对肝癌干细胞的凋亡诱导活性。5-氟尿嘧啶+桔梗皂苷D组HepG2肿瘤干细胞的相对线粒体膜电位(0.21±0.02)显著低于5-氟尿嘧啶组(0.84±0.04,P<0.05),表明桔梗皂苷D通过线粒体途径促进5-氟尿嘧啶对肝癌干细胞的凋亡诱导效应。结论: 桔梗皂苷D通过下调HAX1的表达抑制肝癌干细胞对5-氟尿嘧啶的抵抗性。
英文摘要:
      AIM: To investigate the role of platycodin D in inhibiting the resistance of liver cancer stem cells to 5-fluorouracil. Methods: MTT assay and Annexin V staining were performed to investigate the effect of platycodin D and 5-fluorouracil on cell viability and apoptosis in HepG2 cancer stem cells. Western blot analysis was performed to investigate the effect of platycodin D on regulating the expression of HAX1 in HepG2 cancer stem cells. JC-1 staining, Annexin V staining and western blot analysis was performed to investigate the apoptotic pathway in HepG2 cancer stem cells treated with platycodin D and 5-fluorouracil. Results: Cell viability inhibitory rate of HepG2 cancer stem cells treated with 5 ?mol/L 5-fluorouracil is 29.1±2.4, which is significantly lower than the routine HepG2 cells (72.7±5.2, P<0.05). Cell viability inhibitory rate and apoptotic rate of HepG2 cancer stem cells co-treated with 5-fluorouracil plus platycodin D are 66.7±3.4 and 33.9±2.1, respectively. They are significantly higher than the cell viability inhibitory rate (28.7±1.8, P<0.05) and apoptotic rate (8.9±0.6, P<0.05) of HepG2 cancer stem cells treated with 5-fluorouracil alone. Relative expression of HAX1 in platycodin D treatment group (0.24±0.02) is significantly lower than that in the control group (0.78±0.05, P<0.05). It suggests that platycodin D down-regulates the expression of HAX1 in HepG2 cancer stem cells. Apoptotic rate in 5-fluorouracil + platycodin D + HAX1 plasmid treatment group (10.1±0.7) is significantly lower than that in the 5-fluorouracil + platycodin D group (34.8±2.2, P<0.05). It suggests that platycodin D enhances 5-fluorouracil-induced apoptosis by down-regulating the expression of HAX1 in HepG2 cancer stem cells. Relative mitochondrial membrane potential in 5-fluorouracil + platycodin D treatment group (0.21±0.02) is significantly lower than that in the 5-fluorouracil group (0.84±0.04, P<0.05). It suggests that platycodin D enhances 5-fluorouracil-induced apoptosis through mitochondrial pathway in HepG2 cancer stem cells. Conclusion: Platycodin D inhibits the resistance of liver cancer stem cells to 5-fluorouracil via down-regulating the expression of HAX1.
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