ABT737 reverses cisplatin resistance by targeting glucose metabolism of human ovarian cancer cells.

ABT737 reverses cisplatin resistance by targeting glucose metabolism of human ovarian cancer cells. Int J Oncol. 2018 Jul 09;: Authors: Xu Y, Gao W, Zhang Y, Wu S, Liu Y, Deng X, Xie L, Yang J, Yu H, Su J, Sun L Abstract The poor prognosis and high mortality of patients with ovarian cancer result in part from their poor response to platinum-based chemotherapy. However, the precise mechanism behind cisplatin resistance is still not fully understood. In the present study, the authors explored the mechanism of resistance to cisplatin from the perspective of glucose metabolism in human ovarian cancer. The experiments using genetically matched ovarian cancer cell lines SKOV3 (cisplatin-sensitive) and SKOV3/DDP (cisplatin-resistant) in the present study provided some important findings. First, in comparison to SKOV3 cells, SKOV3/DDP cells exhibited decreased dependence on aerobic glycolysis and an increased demand for glucose. Secondly, the stable overexpression of Bcl‑2 and ability to shift metabolism towards oxidative phosphorylation (OXPHOS) in SKOV3/DDP cells were associated with increased oxygen consumption. Furthermore, the metabolic characteristic of elevated OXPHOS primarily comprised most mitochondrial‑derived reactive oxygen species (ROS) and, at least in part, contributed to the slight pro-oxidant state of SKOV3/DDP cells in turn. Thirdly, SKOV3/DDP cells reset the redox balance by overexpressing the key enzyme glucose 6-pho...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research