Targeting the Bcl-2 family and P-glycoprotein reverses paclitaxel resistance in human esophageal carcinoma cell line.

Abstract

Paclitaxel (PTX) is one of the most effective drugs used in the treatment of esophageal cancer, however, paclitaxel resistance represents a key limitation during the treatment process. In this study, we investigated the changes of Bcl-2 family members in the moderate paclitaxel-resistance of esophageal carcinoma EC109/PTX cells both in vitro and in vivo. Moreover, we evaluated the reversal effect using siRNAs and the recombinant inhibitor TW37 targeting Bcl-2, Bcl-XL and Mcl-1. Our findings show that downregulation of Bcl-2, Bcl-XL and Mcl-1 can significantly promote EC109/PTX cell apoptosis and reduce the EC109/PTX cell resistance index (RI). Furthermore, TW37 in combination with a P-gp inhibitor can synergistically reverse the paclitaxel resistance in EC109/PTX cells. These results suggest that targeting of the Bcl-2 family and P-gp is capable of reversing the resistance in EC109/PTX cells and the two-inhibitor combination may be a novel treatment strategy for resistant esophageal cancer.