论文部分内容阅读
目的:探索在低氧状态下熊果酸对结肠癌细胞化疗增敏的作用及其机制。创新点:首次发现了熊果酸对结肠癌细胞株有化疗增敏作用,这种效果与抑制HIF-1α和MDR1相关。熊果酸在低氧条件下还能抑制肿瘤新生血管生成。方法:分别在常氧和乏氧状态下,在三种结肠癌细胞株RKO、Lo Vo和SW480对5-FU和奥沙利铂的细胞增殖和凋亡实验中,观察熊果酸对提高结肠癌细胞化疗的敏感性(图1和2)。通过定量实时聚合酶链反应和免疫印迹评估HIF-1α、MDR1和血管内皮生长因子(VEGF)的基因转录和蛋白表达水平(图3和4)。通过体外血管形成实验来评价熊果酸对新生血管抑制作用(图5)。结论:熊果酸在乏氧状态下抑制HIF-1α的积累和MDR1的基因和蛋白表达,并抑制新生VEGF的表达,同时对结肠癌细胞化疗有增敏作用。
Objective: To explore the effect and mechanism of ursolic acid on chemosensitivity of colon cancer cells under hypoxia condition. Innovation: Ursolic acid has been found for the first time in chemosensitizing colon cancer cell lines, and this effect is associated with inhibition of HIF-1α and MDR1. Ursolic acid can also inhibit tumor angiogenesis in hypoxic conditions. Methods: In the experiments of proliferation and apoptosis of 5-FU and oxaliplatin in three kinds of colon cancer cell lines RKO, Lo Vo and SW480 under normoxia and hypoxia respectively, Cancer cell chemosensitivity (Figures 1 and 2). The gene transcription and protein expression levels of HIF-la, MDR1 and vascular endothelial growth factor (VEGF) were assessed by quantitative real-time polymerase chain reaction and Western blotting (Figures 3 and 4). The effect of ursolic acid on neovascularization was evaluated by in vitro angiogenesis experiments (Figure 5). CONCLUSION: UA inhibits the accumulation of HIF-1α and the expression of MDR1 gene and protein in hypoxic condition, and inhibits the expression of newborn VEGF. It also sensitizes colon cancer cells to chemotherapy.