Involvement of CHK1 pathway in protecting cells from taxotere-induced killing

5326

Taxotere is an anticancer agent with demonstrated activity in a variety of solid tumors. Taxotere affects tubulin polymerization and interferes with mitotic transition. These changes activate the apoptosis process and elicit cytotoxicity. However, these changes can also slow down cell cycle progression by activating checkpoints that provide time for repair and thus reduce the cytotoxicity. Therefore, the cellular response to taxotere-cytotoxicity can impact the expected therapeutic efficacy. To date, the mechanism by which cell cycle checkpoints impact taxotere cytotoxicity remains unclear. Here our preliminary data show that a CHK1 over-expressing cell line, A1-5 cells (JBC, 276:17693, 2001) were more resistant to taxotere cytotoxicity than its counterpart cell line, B4 cells. Validation of the gene-specific effect was obtained when CHK1 protein expression was suppressed by siRNA and the taxotere resistance was eliminated in A1-5 cells. These data suggest that CHK1 pathway-regulated checkpoint can be important in protecting cells from the taxotere cytotoxicity. This work was supported by a grant from Aventis.