Inhibition of anti-apoptotic signals in prostate cancer cells by CCL25 blockade enhances the cytotoxic effects of etoposide (98.1)
| Autor: | Praveen K Sharma, Rajesh Singh, John W Eaton, James W Lillard, Jr., Kristian R Novakovic, William E Grizzle, Shailesh Singh |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 182:98.1-98.1 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.182.supp.98.1 |
| Popis: | Despite of current advancement in treatment and management of prostate cancer (PCa); it is still remaining the second leading cause of cancer-related deaths among men in the US. Current chemotherapeutic regimens provided palliative benefit but relatively modest survival advantage for the patients with hormone refractory PCa. This results in an initial response, but always followed by relapse due to chemoresistance and relatively low rate of apoptosis in PCa cells. Therefore, better efficacy of chemotherapeutics can be achieved by combining additional agents, which can block the mechanisms responsible for this low apoptosis rate. We have previously shown that CCR9 is expressed by the PCa cells and support the mechanisms involved in PCa metastasis. In this study, we have demonstrated that CCR9 and its natural ligand; CCL25 interaction up regulates anti-apoptotic proteins and promotes cell survival. Inhibition of these interactions using antibody blocked enhanced the etoposide-induced apoptosis of PCa cells in vitro and reduces tumor burden in vivo. Therefore, targeting this axis with chemotherapeutic agents may enhance the therapeutic outcomes of PCa. [Supported by funds from DOD PCRP Award W81XWH-06-1-0521] |
| Databáze: | OpenAIRE |
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