Source abstract
Abstract
Platinum (Pt)-based chemotherapy drugs such as cisplatin are the first line and core options for the treatment of ovarian cancer (OC), while cisplatin resistance has a worse prognosis and low 5 year survival rate for patients. Chemotherapeutic drugs synthesized from nanomaterials have shown great potential in biomedicine; however, research into their application for OC resistance is rarely discussed. This study is proposed to elucidate the anti-tumor effects of polyethylenimine (PEI)-caged platinum nanoclusters (Pt NCs) on cisplatin-resistant OC. The results of confocal microscopy showed that Pt NCs entered cisplatin-resistant OC cells dose-dependently and aggregated both in the cytoplasm and inside the nucleus. Subsequently, according to the results of CCK8 assay, wound healing assay, clone formation assay, Transwell assay, Ki-67 immunofluorescence assay, and flow cytometry assay, the proliferation and migration of cisplatin-resistant OC cells were inhibited by Pt NCs, as well as their apoptosis was promoted. In addition, we validated the anti-tumor effect of Pt NCs on regulating autophagy via monodansylcadaverine (MDC) staining, transmission electron microscopy observation of the autophagic ultrastructure, LC3-II-GFP and P62-GFP adenovirus single-label immunofluorescence, and western blotting; meanwhile, the role of Pt NCs in adjusting autophagy through modulation of the PI3K-AKT-mTOR signaling was verified. Based on these results, it appears that cisplatin-resistant OC cells can undergo apoptosis when Pt NCs activate autophagy by inhibiting the PI3K/AKT/mTOR pathway, exhibiting a promising potential of Pt NCs in the development of a novel chemotherapeutic agent for patients suffering from cisplatin-resistant OC.
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Affiliations
Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University, 7 Rehabilitation Front Street, Zhengzhou 450052, China
Department of Center for Clinical Single Cell Biomedicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, No. 7 Weiwu Street, Zhengzhou 450003, China
Department of Light Chemical Engineering, School of Textiles, Zhongyuan University of Technology, No. 41 Zhongyuan Road (M), Zhengzhou 450007, China
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, No.45 Changchun Street, Beijing 100053, China
Funding
Zhongyuan University of Technology · Science and Technology Department of Henan Province · Henan Province Foundation for University Key Teacher · National Natural Science Foundation of China · Henan Province Medical Science and Technology Project