[关键词]
[摘要]
以牡丹籽油为研究对象,结肠癌细胞HCT116为模型,评估了牡丹籽油对HCT116结肠癌细胞体外增殖和周期的影响,并对其分子机理进行了初步的研究。利用MTS实验、蛋白蛋印迹等检测了结肠癌细胞在增殖、迁移和分子水平上的变化。结果表明:牡丹籽油能显著抑制HCT116细胞的增殖和迁移能力;当牡丹籽油的浓度达到100 μg/mL时,细胞周期相关基因p15、p21、p53的mRNA相对表达量相比对照组(Con)分别上升了5.49、4.56和3.73倍,具有极显著性差异(p<0.01)。提示牡丹籽油能调控细胞周期G1/S期关键靶基因的表达,使细胞周期阻滞在G1/S期。牡丹籽油也能抑制MAPK信号通路的激活,且能显著抑制其下游转录因子AP-1和NF-κB的活性。结果提示牡丹籽油可能通过抑制MAPK信号通路/AP-1和NF-κB活性下调,调控细胞周期相关基因的表达,从而抑制结直肠癌细胞的增殖,课题研究将为功能性抗癌类食用植物油的开发提供科学的理论基础。
[Key word]
[Abstract]
Using peony seed oil as the research object and colon cancer cells HCT116 as the model, the effect of peony seed oil on the in vitro proliferation and cell cycle of HCT116 cells were evaluated, and the underlying molecular mechanism was preliminary studied. The changes in proliferation, migration and molecular level of colon cancer cells were detected by the MTS and Western blotting assays. The results showed that peony seed oil inhibited significantly the proliferation and migration abilities of HCT116 cells. When the concentration of peony seed oil reached 100 μg/mL, the relative mRNA expression of cell cycle-associated genes, p15, p21 and p53, increased by 5.49, 4.56 and 3.73 times, respectively, with extremely significant differences (p<0.01) compared with the control group. These results suggested that peony seed oil could regulate the expression of key target genes associated with the G1/S period of cell cycle, enabling the cell cycle blocked in G1/S transition period. Peony seed oil could also inhibit the activation of the MAPK signaling pathway, as well as the activities of its downstream transcription factors, AP-1 and NF-κB. The results suggest that peony seed oil may inhibit the down-regulation of AP-1 and NF-κB activities for the MAPK signaling pathway, and regulate the expression of cell cycle-related genes, thereby inhibiting the proliferation of colon cancer cells. The research will provide a scientific theoretical basis for the development of functional vegetable oil with anti-cancer activity.
[中图分类号]
[基金项目]
湖南省自然科学基金(2018JJ2672);湖南省研究生科研创新项目(CX2018B457;20192040);中南林业科技大学研究生科技创新基金(20183010;CX20190629)