CAJ | 학술논문

目的：研究化合物Jaridonin抗肿瘤作用的选择性并探讨其可能机制。方法采用噻唑蓝( MTT)法检测Jaridonin抑制细胞增殖的作用；使用倒置荧光显微镜进行细胞形态学研究；流式细胞术检测细胞凋亡及细胞内活性氧( ROS )水平；Western blot法检测Jaridonin对细胞凋亡通路相关蛋白表达的影响。结果 Jaridonin 能明显抑制胃癌细胞 MGC-803的增殖,且呈较好的浓度依赖性,而对人正常胃粘膜细胞GES-1的增殖没有明显影响；Jaridonin 作用于 MGC-803后明显引起Bax表达上调、线粒体膜电位下降、细胞色素C释放、caspase-3激活以至细胞凋亡,而对GES-1凋亡的影响并不明显；Jaridonin诱导MGC-803活性氧水平持续增加,而GES-1内活性氧水平先迅速上升,6h后下降至基础水平；外源性GSH几乎可以完全逆转Jaridonin对MGC-803的抑制作用。结论 Jaridonin选择性的抑制胃癌细胞的增殖并诱导线粒体途径参与的凋亡,其选择性机制可能与Jaridonin直接作用于氧化还原系统引起胞内活性氧水平升高有关。
목적：연구화합물Jaridonin항종류작용적선택성병탐토기가능궤제。방법채용새서람( MTT)법검측Jaridonin억제세포증식적작용；사용도치형광현미경진행세포형태학연구；류식세포술검측세포조망급세포내활성양( ROS )수평；Western blot법검측Jaridonin대세포조망통로상관단백표체적영향。결과 Jaridonin 능명현억제위암세포 MGC-803적증식,차정교호적농도의뢰성,이대인정상위점막세포GES-1적증식몰유명현영향；Jaridonin 작용우 MGC-803후명현인기Bax표체상조、선립체막전위하강、세포색소C석방、caspase-3격활이지세포조망,이대GES-1조망적영향병불명현；Jaridonin유도MGC-803활성양수평지속증가,이GES-1내활성양수평선신속상승,6h후하강지기출수평；외원성GSH궤호가이완전역전Jaridonin대MGC-803적억제작용。결론 Jaridonin선택성적억제위암세포적증식병유도선립체도경삼여적조망,기선택성궤제가능여Jaridonin직접작용우양화환원계통인기포내활성양수평승고유관。
Aim To investigate Jaridonin′s selective killing of cancer cells and explore the related molecular mechanism. Methods After treatment by Jaridonin for 24 h, the effect of Jaridonin on the cell viability was examined using MTT assay. The effect of Jaridonin on cytomorphology and mitochondrial membrane poten-tial (Δψm) was observed by a fluorescence microsco-py. The apoptosis of cell lines treated with Jaridonin, as well as the level of reactive oxygen species ( ROS ) was analyzed by flow cytometry. Expression of the pro-teins related with mitochondria apoptosis pathways was detected by Western blot. Results Jaridonin caused strong antiproliferative and apoptotic effects on MGC-803 cells, but there were not remarkable effects on GES-1 cells. Furthermore, the expression of Bax was up-regulated, and the release of cytochrome c from mi-tochondria to cytosol was also promoted in MGC-803 cells treated by Jaridonin. The cleavage of caspase-3 in MGC-803 cells was also observed. Jaridonin increased persistently intracellular levels of ROS in MGC-803 cells, whereas the level of ROS in GES-1 rose in the first stage, and then decreased, and dropped to the basic level after 6 h. More interestingly, Jaridonin-in-duced ROS accumulation and the inhibition of MGC-803 cell proliferation were almost completely attenuated in the presence of GSH. Conclusions Jaridonin se-lectively kills cancer cells and induces apoptosis in MGC-803 through ROS-mediated mitochondrial dam-age.