BAX通过一条不依赖p53的途径增强紫杉醇诱导的细胞凋亡。
BAX enhances paclitaxel-induced apoptosis through a p53-independent pathway.
作者信息
Strobel T, Swanson L, Korsmeyer S, Cannistra S A
机构信息
Division of Neoplastic Disease Mechanisms, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14094-9. doi: 10.1073/pnas.93.24.14094.
To investigate the role of BAX in chemotherapy-induced apoptosis, we transfected the SW626 human ovarian cancer cell line, which lacks functional p53, with a cDNA encoding for murine BAX. Immunoblotting revealed that BAX transfectants expressed a mean of 10-fold increased levels of BAX compared with neo-transfected control clones, with similar levels of BCL-2 and BCL-xL. The cytotoxicity of paclitaxel, vincristine, and doxorubicin was significantly enhanced in BAX transfectants compared with control clones, whereas the cytotoxicity profile of carboplatin, etoposide, and hydroxyurea was unchanged. Increased paclitaxel-induced cytotoxicity of BAX clones was associated with enhanced apoptosis, as assessed by morphologic and flow cytometric criteria. These data suggest that sufficient levels of BAX may bypass the need for upstream molecules such as p53 in the process of chemotherapy-induced apoptosis.
为了研究BAX在化疗诱导的细胞凋亡中的作用，我们用编码小鼠BAX的cDNA转染了缺乏功能性p53的SW626人卵巢癌细胞系。免疫印迹显示，与新转染的对照克隆相比，BAX转染子表达的BAX水平平均增加了10倍，而BCL-2和BCL-xL的水平相似。与对照克隆相比，BAX转染子中紫杉醇、长春新碱和阿霉素的细胞毒性显著增强，而卡铂、依托泊苷和羟基脲的细胞毒性谱没有变化。通过形态学和流式细胞术标准评估，BAX克隆中紫杉醇诱导的细胞毒性增加与细胞凋亡增强有关。这些数据表明，在化疗诱导的细胞凋亡过程中，足够水平的BAX可能绕过对上游分子如p53的需求。
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