Fas-mediated signaling enhances sensitivity of human soft tissue sarcoma cells to anticancer drugs by activation of p38 kinase

WeiWei Li, Joseph R Bertino
2002 Molecular Cancer Therapeutics  
Sensitivity of human soft tissue sarcoma (STS) cells to methotrexate, doxorubicin, and paclitaxel was examined after cells were pretreated with CH-11, an agonistic anti-Fas antibody. A subtoxic dose (6 ng/ml) of CH-11 sensitized STS cells but not normal fibroblast cells to these anticancer drugs. CH-11 increased cytochrome c release and consequent activation of caspase-9, independent of caspase-8 and increased p38 activation. Addition of SB203580, a specific inhibitor of p38, resulted in a
more » ... resulted in a decrease in activation of this kinase and abrogation of enhanced chemosensitivity (doxorubicin and paclitaxel) by CH-11. These results demonstrate that stimulation of the Fas pathway by a subtoxic dose of a Fas agonist can selectively enhance sensitivity of STS cells to certain chemotherapeutic agents through activation of p38.
pmid:12516968 fatcat:6vvl4xmxmrcv7gnhmfy5i5aceu