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1, 25-二羟维生素D3对人结肠癌细胞凋亡和自噬的影响及机制研究

Study in effects of 1, 25-dihydroxyvitamin D3 on apoptosis and autophagy of colon cancer cells and its mechanism

    摘要
  • 摘要:
      目的  观察1，25-二羟维生素D31，25-（OH）2D3对人结肠癌HCT-116细胞凋亡和自噬的影响并初步探讨其机制。
      方法  体外培养人结肠癌细胞HCT-116，分成对照组、低剂量组、中剂量组、高剂量组和联合组1，25-（OH）2D3高剂量联合腺苷单磷酸活化蛋白激酶（AMPK）抑制剂共5组，观察并比较各组细胞凋亡和自噬情况。
      结果  低剂量组、中剂量组、高剂量组的HCT-116细胞凋亡程度、自噬程度及cleaved Caspase3、cleaved Caspase8、LC3Ⅱ/LC3Ⅰ、Beclin-1、p-AMPK蛋白表达水平高于对照组，p-mTOR蛋白表达水平低于对照组，差异有统计学意义（P < 0.05）。联合组的HCT-116细胞凋亡程度、自噬程度及cleaved Caspase3、cleaved Caspase8、LC3Ⅱ/LC3Ⅰ、Beclin-1、p-AMPK蛋白表达水平低于高剂量组，p-mTOR蛋白表达水平高于高剂量组，差异有统计学意义（P < 0.05）。
      结论  1，25-（OH）2D3可通过调控AMPK/mTOR信号通路增强结肠癌细胞凋亡和自噬，发挥抗肿瘤作用。

     

    Abstract:
      Objective  To observe the effects of 1, 25 dihydroxyvitamin D31, 25-(OH)2D3 on apoptosis and autophagy of human colon cancer HCT116 cells and explore its mechanism.
      Methods  HCT-116 cells were cultured in vitro and divided into control group, low-dose group, medium-dose group, high-dose group and combined grouphigh-dose 1, 25-(OH)2D3 combined with adenosine monophosphate activated protein kinase (AMPK) inhibitor. Apoptosis and autophagy were observed and compared in each group.
      Results  The degrees of apoptosis and autophagy, the expression levels of cleaved Caspase 3, cleaved Caspase 8, LC3Ⅱ/LC3Ⅰ, Beclin-1 and p-AMPK proteins in HCT-116 cells in low-dose group, medium-dose group and high-dose group were significantly higher, and the expression level of p-mTOR protein was significantly lower compared with those in the control group (P < 0.05). The degrees of apoptosis and autophagy, the expression levels of cleaved Caspase 3, cleaved Caspase 8, LC3Ⅱ/LC3Ⅰ, Beclin-1 and p-AMPK proteins in HCT-116 cells in the combined group were significantly lower, while the expression level of p-mTOR protein was significantly higher compared with those in the high-dose group (P < 0.05).
      Conclusion  1, 25-(OH)2D3 can enhance apoptosis and autophagy of colon cancer cells by regulating AMPK/mTOR signaling pathway thereby playing anti-tumor roles.

     

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