HIF-1 dependent reversal of cisplatin resistance via anti-oxidative nano selenium for effective cancer therapy

Publication date: 15 January 2020Source: Chemical Engineering Journal, Volume 380Author(s): Xiaojuan Zhang, Chuanchuan He, Ruicong Yan, Yan Chen, Pengxuan Zhao, Minsi Li, Ting Fan, Tan Yang, Yao Lu, Jun Luo, Xiang Ma, Guangya XiangAbstractThe clinical efficacy of cisplatin (DDP) treatment is largely limited by cisplatin resistance, which is related to the activation of hypoxia-inducible factor 1 (HIF-1). The HIF-1 activation can be induced by low oxygen availability as well as chemotherapeutics in a reactive oxygen species (ROS) dependent manner. Here, instead of the traditional ROS elevation strategy, we designed a chitosan-coated selenium/DDP (CSP) nanoparticle to deplete ROS for circumventing acquired cisplatin resistance. The antioxidative selenium nanoparticles were demonstrated to eliminate cisplatin-induced ROS, and further prevent HIF-1 activation accompanied with cisplatin treatment. A series of cisplatin resistance-associated proteins including glutamate-cysteine ligase modifier subunit (GCLM) and multidrug resistance-associated proteins (MRPs) expression were downregulated in a HIF-1α-dependent manner. And in vitro and in vivo experiments showed that CSP nanoparticles exhibited enhanced antitumor efficacy to cisplatin-resistant A549/DDP lung cancer cell lines and xenografts. These results proved that the side effects of treatment-induced ROS in HIF-1 activation and cisplatin-resistance could be significantly reversed by a selenium nanovehicle, which may possess br...
Source: Chemical Engineering Journal - Category: Chemistry Source Type: research