Bcl-2-enhanced efficacy of microtubule-targeting chemotherapy through Bim overexpression: implications for cancer treatment.

ABSTRACT: Bcl-2 is commonly overexpressed in tumors, where it is often associated with unfavorable outcome. However, it has also been linked to a favorable sensitivity to microtubule-targeting agents (MTAs). We show that Bcl-2-overexpressing lung and breast cancer cells were more sensitive to both paclitaxel and vinorelbine. Bcl-2 over-expression also significantly potentiated in vivo efficacy of paclitaxel, in terms of tumor volume decrease and survival benefits, in models of nude mice bearing lung cancer xenografts. To further investigate this favorable effect of Bcl-2, a genomic approach was taken. It revealed that Bcl-2 overexpression induced up-regulation of the proapoptotic protein Bim in lung cancer cells and that, conversely, Bcl-2 silencing decreased Bim expression level. A gene regulation

SUBMITTER: Savry A 

PROVIDER: S-EPMC3556938 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature