α2β1 Integrin specific inhibitor BTT-3033 promotes paclitaxel-induced apoptosis in human ovarian cancer cells.

Background and purpose: The new plan of using molecular targeted agents in combination with cytotoxic drugs may represent a promising strategy to increase the efficacy of chemotherapy. Hence, we examined whether α2β1 integrin-specific inhibitor, BTT-3033, could modulate the susceptibility of OVCAR3 and SKOV3 ovarian cancer cells to paclitaxel (PTX). Experimental approach: Ovarian cancer cell lines were treated with BTT-3033 and different concentrations of PTX. To determine the mechanisms involved in the PTX/BTT-3033 combination-induced cell death, cell viability, apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and caspase-3 activity were evaluated. Findings/Results: Both BTT-3033 (≥ 1 μM) and PTX (≥ 0.01 μM) suppressed the proliferation of OVCAR3 and SKOV3 cells in a concentration-related manner. Pretreatment with BTT-3033 (1 μM), followed by PTX-induced synergistic antiproliferative effects, decreased the IC Conclusion and implications: BTT-3033 has demonstrated the ability to enhance the susceptibility of ovarian cancer cells to PTX by inducing MMP loss, ROS production, and mitochondrial apoptosis, therefore this combination therapy might represent a promising strategy for ovarian cancer treatment.