中国药理学通报2012，Vol.28Issue(6)：828-832,5.DOI:10.3969/j.issn.1001-1978.2012.06.022
一种新的吲哚咔唑类化合物(ZWM233)的体外抗肿瘤作用及机制探讨
Anticancer effects of ZWM233 in vitro and its mechanisms
刘书娟 1戚欣 1朱伟明 1李静1
作者信息
- 1. 中国海洋大学医药学院,海洋药物教育部重点实验室分子药理室,山东,青岛,266003
- 折叠
摘要
Abstract
Aim To investigate the antiproliferation effects of ZWM233 in a variety of cancer cell lines and the apoptosis mechanisms of K562 cells in vitro. Methods Inhibitory effects of ZWM233 on proliferation of a variety of cancer cell lines were analyzed by MTT method. The changes of K562 cell cycle was detected by flow cytometry. Apoptosis was determined by An-nexinV/PI dual staining. The expressions of bax, bcl-2, Caspase-3, Caspase-9, PARP, ERK, p-ERK, JNK, p-JNK,GSK-3p,p-GSK-3β and PKC isotypes were detected by Western blotting assay. Results ZWM233 potentially inhibited proliferation of a variety of cancer cell lines,among which K562 cells were the most significant (IC50 was 2. 81 μmol ·L-1). FCM analysis revealed that ZWM233 induced k562 cells toward apop-tosis in a dose-dependent manner and the cell cycle was blocked at G2/M phase. After treated with ZWM233 for 24 h, ZWM233 could down-regulate bcl-2 and activate Caspase-9 and Caspase-3 to cleave the downstream substrate PARP to induce K562 cells apoptosis. Western blotting also showed that ZWM233 could down-regulate PKC8, p-ERKl/2 and p-GSK-30 and reversely regulate p-JNK in a dose-dependent manner. Conclusion ZWM233 potentially inhibits proliferation in K562 leukemia cells in vitro and induces apoptosis via activating the mitochondrial pathways. Its mechanism is involved in the down-regulation of pkc8 as well as its downstream p-GSK-3β and p-ERKl/2.关键词
ZWM233/K562/细胞周期/细胞凋亡/机制/PKCKey words
ZWM233/ K562/ cell cycle/ apoptosis/ mechanism/ PKC分类
医药卫生引用本文复制引用
刘书娟,戚欣,朱伟明,李静..一种新的吲哚咔唑类化合物(ZWM233)的体外抗肿瘤作用及机制探讨[J].中国药理学通报,2012,28(6):828-832,5.
