Author/Authors :
Costantino، نويسنده , , Eleonora and Maddalena، نويسنده , , Francesca and Calise، نويسنده , , Serena and Piscazzi، نويسنده , , Annamaria and Tirino، نويسنده , , Virginia and Fersini، نويسنده , , Alberto and Ambrosi، نويسنده , , Antonio and Neri، نويسنده , , Vincenzo and Esposito، نويسنده , , Franca and Landriscina، نويسنده , , Matteo، نويسنده ,
Abstract :
TRAP1 is a component of a pro-survival mitochondrial pathway up-regulated in tumor cells. The evaluation of TRAP1 expression in 26 human colorectal carcinomas showed up-regulation in 17/26 tumors. Accordingly, TRAP1 levels were increased in HT-29 colorectal carcinoma cells resistant to 5-fluorouracil, oxaliplatin and irinotecan. Thus, we investigated the role of TRAP1 in multi-drug resistance in human colorectal cancer. Interestingly, TRAP1 overexpression leads to 5-fluorouracil-, oxaliplatin- and irinotecan-resistant phenotypes in different neoplastic cells. Conversely, the inhibition of TRAP1 activity by TRAP1 ATPase antagonist, shepherdin, increased the sensitivity to oxaliplatin and irinotecan in colorectal carcinoma cells resistant to the single agents. These results suggest that the increased expression of TRAP1 could be part of a pro-survival pathway responsible for multi-drug resistance.
Keywords :
oxidative stress , Chemoresistance , TRAP1 , apoptosis , chemotherapy , colorectal carcinoma
