δ-生育三烯酚诱导人结肠癌细胞SW620副凋亡作用研究

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目的探讨δ-生育三烯酚诱导人结肠癌细胞SW620副凋亡作用及其机制。方法以MTT试验观察0~30μmol/Lδ-生育三烯酚对人结肠癌细胞SW620及人胃黏膜上皮细胞GES-1细胞增殖作用的影响,观察1.0μmol/L放线菌酮(CHX)对15μmol/Lδ-生育三烯酚诱导人结肠癌细胞SW620副凋亡的抑制作用。以Western blot检测0~20μmol/Lδ-生育三烯酚对人结肠癌细胞SW620中增殖与凋亡关键信号通路Notch1及Jagged1蛋白表达的影响。以透射电镜检测15μmol/Lδ-生育三烯酚对人结肠癌细胞SW620副凋亡的形态学特征的影响。结果与溶剂对照组相比,用不同剂量的δ-生育三烯酚(终浓度为5、10、15、20、25、30μmol/L)分别作用于SW620及GES-1细胞24 h,SW620细胞存活率下降(P<0.05),而GES-1细胞存活率未见明显下降(P>0.05)。提前给予1.0μmol/L CHX处理的细胞,经15μmol/L生育三烯酚诱导SW620凋亡作用24 h后,SW620存活率较单独加入生育三烯酚作用的细胞存活率增高(P<0.05)。1.0μmol/L CHX和15μmol/Lδ-生育三烯酚共同作用于SW620细胞24 h后,Notch1、Jagged1蛋白表达量与对照组相比分别上升41.8%、41.9%。透射电镜下15μmol/Lδ-生育三烯酚作用24 h后,SW620细胞在形态学上呈现副凋亡特征,1.0μmol/L CHX能抑制生育三烯酚诱导SW620的副凋亡作用。结论δ-生育三烯酚能诱导SW620细胞paraptosis样副凋亡,并且这一过程可以被CHX抑制。 Objective To investigate the apoptosis of human colon cancer cell line SW620 induced by δ-tocotrienol and its mechanism. Methods MTT assay was used to observe the effects of 0 ~ 30μmol / L δ-tocotrienol on the proliferation of human colon cancer cell line SW620 and human gastric mucosal epithelial cells. The effects of 1.0μmol / L cycloheximide on the proliferation of human colon cancer cell line SW620 and human gastric mucosal epithelial cells GES- / Lδ-tocotrienol-induced apoptosis in human colon cancer cell line SW620. The effect of 0 ~ 20μmol / L δ-tocotrienol on the expression of Notch1 and Jagged1, the key signal pathway of proliferation and apoptosis in human colon carcinoma cell line SW620 was detected by Western blot. The effects of 15μmol / L δ-tocotrienol on morphological characteristics of apoptosis of human colon cancer cell line SW620 were detected by transmission electron microscopy. Results Compared with the solvent control group, SW620 and GES-1 cells were treated with different doses of δ-tocotrienol (final concentrations of 5, 10, 15, 20, 25 and 30 μmol / L) The survival rate decreased (P <0.05), while the survival rate of GES-1 cells was not significantly decreased (P> 0.05). After pretreatment with 1.0 μmol / L CHX for 24 h, the survival rate of SW620 cells was higher than that of cells treated with tocotrienol alone (P <0.05) after 15 μmol / L tocotrienol induced apoptosis of SW620 cells. Compared with the control group, the expression of Notch1 and Jagged1 protein increased by 41.8% and 41.9% respectively after SW620 cells were treated with 1.0μmol / L CHX and 15μmol / L δ-tocotrienol for 24 hours. After treated with 15μmol / L δ-tocotrienol for 24 h, the SW620 cells showed the morphological characteristics of apoptosis, and 1.0 μmol / L CHX could inhibit the apoptosis of SW620 cells induced by tocotrienols. Conclusion δ-tocotrienol can induce paraptosis-like apoptosis in SW620 cells, and this process can be inhibited by CHX.
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