δ-生育三烯酚诱导人结肠癌细胞SW620副凋亡作用研究

δ-Tocotrienol-induced paraptosis-like death of human colon cancer SW620 cells

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MTr试验观察0～30μmol／L δ-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/L δ-生育三烯酚诱导人结肠癌细胞SW620副凋亡的抑制作用。以Westernblot检测0～20μmol/L δ-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Notch 1及Jagged1蛋白表达的影响。以透射电镜检测15μmol／L δ-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24h，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／LCHX处理的细胞，经15μmol／L生育三烯酚诱导SW620凋亡作用24h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／L δ-生育三烯酚共同作用于SW620细胞24h后，Notchl、Jaggedl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／L δ-生育三烯酚作用24h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6一生育三烯酚能诱导SW620细胞paraptosis样副凋亡，并且这一过程可以被CHX抑制。

Objective To investigate δ-tocotrienol-induced paraptosis in human colon cancer cell SW620 and its mechanism.Methods The effect of 0-30 μmol/L δ-tocotrienol on cell proliferation of colon cancer cells SW620 and human gastric epithelial cell line GES-1 was observed by MTT assay. Tthe inhibitition of CHX on 1.0 μmol/L δ-tocotrienol-induced paraptosis in colon cancer cells SW620 was observed by MTT assay. The expression of key proteins Notch1 and Jagged1 of Notch-signaling pathway in colon cancer cells SW620 exposed to 0-20 μmol/L δ-tocotrienol was detected by Western blot.Ultramicroscopic morphological characteristics for 1.0 μmol/L δ-tocotrienol-induced paraptosis of colon cancer cells SW620 was observed by transmission electron microscope. Results With the increase of δ-tocotrienol concentrations, the human colon cancer cell SW620 viability was significant decreased than the control group（P〈 0.05）, and there was no significant decrease than the control group of the human gastric epithelial cell line GES-1（P〈 0.05）. After pre-treatment with 1.5 μmol/L CHX, the cell viability was significantly increased compared with the effect of δ-tocotrienol（P〈 0.05）. The expressions of Notch signaling pathway key proteins Notch1 and Jagged1 were increased in certain dose range by Western blot. 1.0 μmol/L CHX could inhibit a paraptosis-like death of human colon cancer cell SW620 of ultramicroscopic findings. Conclusion δ-tocotrienol may induce a paraptosis-like death of human colon cancer cell SW620,which may be inhibited by CHX.