BAX ENHANCES PACLITAXEL-INDUCED APOPTOSIS THROUGH A P53-INDEPENDENT PATHWAY

To investigate the role of BAX in chemotherapy-induced apoptosis, we t ransfected the SW626 human ovarian cancer cell line, which lacks funct ional p53, with a cDNA encoding for murine BAX. Immunoblotting reveale d that BAX transfectants expressed a mean of 10-fold increased levels of BAX compared with neo-transfected control clones, with similar leve ls of BCL-2 and BCL-X(L). The cytotoxicity of paclitaxel, vincristine, and doxorubicin was significantly enhanced in BAX transfectants compa red with control clones, whereas the cytotoxicity profile of carboplat in, etoposide, and hydroxyurea was unchanged, Increased paclitaxel-ind uced 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 apoptosi s.