1. Venetoclax, a BCL-2 Inhibitor, Enhances the Efficacy of Chemotherapeutic Agents in Wild-Type ABCG2-Overexpression-Mediated MDR Cancer Cells.
- Author
-
Wang, Jing-Quan, Li, Jonathan Y., Teng, Qiu-Xu, Lei, Zi-Ning, Ji, Ning, Cui, Qingbin, Zeng, Leli, Pan, Yihang, Yang, Dong-Hua, and Chen, Zhe-Sheng
- Subjects
- *
ANTINEOPLASTIC agents , *BREAST tumors , *CELL lines , *DRUG resistance in cancer cells , *DRUG synergism , *MOLECULAR structure , *MEMBRANE transport proteins , *PHARMACODYNAMICS - Abstract
Previous studies have shown that small-molecule BCL-2 inhibitors can have a synergistic interaction with ABCG2 substrates in chemotherapy. Venetoclax is a potent and selective BCL-2 inhibitor, approved by the FDA in 2016 for the treatment of patients with chronic lymphocytic leukemia (CLL). This study showed that, at a non-toxic concentration, venetoclax at 10 µM significantly reversed multidrug resistance (MDR) mediated by wild-type ABCG2, without significantly affecting MDR mediated by mutated ABCG2 (R482G and R482T) and ABCB1, while moderate or no reversal effects were observed at lower concentrations (0.5 to 1 µM). The results showed that venetoclax increased the intracellular accumulation of chemotherapeutic agents, which was the result of directly blocking the wild-type ABCG2 efflux function and inhibiting the ATPase activity of ABCG2. Our study demonstrated that venetoclax potentiates the efficacy of wild-type ABCG2 substrate drugs. These findings may provide useful guidance in combination therapy against wild-type ABCG2-mediated MDR cancer in clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF