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Phosphorylation of caspase-9 at Thr125 directs paclitaxel resistance in ovarian cancer.

ABSTRACT: Although paclitaxel is routinely prescribed for the treatment of epithelial ovarian cancer (EOC), paclitaxel resistance is common in EOC and correlates with short survival of patients. A previous pharmacogenomic study revealed the importance of cyclin-dependent kinase 1 (CDK1) activity in a response on paclitaxel. However, a subsequent research showed that the expression level of CDK1 failed to show significant correlation with delayed apoptosis and patient survival. Rather, the expression and phosphorylation of capase-9, the downstream target molecule of CDK1, appeared to determine drug resistance. Our results suggest that treatment with the CDK1 inhibitor alsterpaullone reduces phosphorylation of caspase-9. Its phosphorylation level was dependent on CDK1 activity and it directs paclitaxel resistance. This observation was reproducible in xenografted tumors. Thus, the regulation of caspase-9 may be a novel therapeutic strategy to reverse paclitaxel-induced resistance in ovarian cancer cells.

SUBMITTER: Byun MR

PROVIDER: S-EPMC5787417 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Phosphorylation of caspase-9 at Thr125 directs paclitaxel resistance in ovarian cancer.

Byun Mi Ran MR Choi Jin Woo JW

Oncotarget 20171208 1

Although paclitaxel is routinely prescribed for the treatment of epithelial ovarian cancer (EOC), paclitaxel resistance is common in EOC and correlates with short survival of patients. A previous pharmacogenomic study revealed the importance of cyclin-dependent kinase 1 (CDK1) activity in a response on paclitaxel. However, a subsequent research showed that the expression level of CDK1 failed to show significant correlation with delayed apoptosis and patient survival. Rather, the expression and p ...[more]

PMID: 29416675

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