Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No.639 Zhizaoju Road, Huangpu District, Shanghai, 200011, China.
National Clinical Research Center for Oral Diseases, Shanghai, China.
Cell Mol Biol Lett. 2022 Dec 6;27(1):107. doi: 10.1186/s11658-022-00407-8.
Oral squamous cell carcinoma (OSCC) is a common head and neck cancer, and the incidence of OSCC is increasing. As the mortality of OSCC keeps increasing, it is crucial to clarify its pathogenesis and develop new therapeutic strategies.
Confocal laser scanning microscopy was used to evaluate the uptake of nanoparticles (NPs). The potential functions of USP30 were evaluated by cell counting kit (CCK)-8, flow cytometry, biochemical assay, coimmunoprecipitation, qRT-PCR, and immunoblotting. The antitumor effect of NP-loaded USP30 inhibitor MF-094 was evaluated in vitro and in vivo.
In this study, increased USP30 expression was found in OSCC specimens and cell lines through qRT-PCR and immunoblotting. CCK-8, flow cytometry, and biochemical assay revealed that the deubiquitylated catalytic activity of USP30 contributed to cell viability and glutamine consumption of OSCC. Subsequently, USP30 inhibitor MF-094 was loaded in ZIF-8-PDA and PEGTK to fabricate ZIF-8-PDA-PEGTK nanoparticles, which exhibited excellent inhibition of cell viability and glutamine consumption of OSCC, both in vitro and in vivo.
The results indicated the clinical significance of USP30 and showed that nanocomposites provide a targeted drug delivery system for treating OSCC.
口腔鳞状细胞癌(OSCC)是一种常见的头颈部癌症,其发病率正在上升。由于 OSCC 的死亡率不断上升,阐明其发病机制并开发新的治疗策略至关重要。
使用共聚焦激光扫描显微镜评估纳米颗粒(NPs)的摄取。通过细胞计数试剂盒(CCK)-8、流式细胞术、生化测定、共免疫沉淀、qRT-PCR 和免疫印迹评估 USP30 的潜在功能。在体外和体内评估负载 NP 的 USP30 抑制剂 MF-094 的抗肿瘤作用。
在这项研究中,通过 qRT-PCR 和免疫印迹发现 USP30 在 OSCC 标本和细胞系中的表达增加。CCK-8、流式细胞术和生化测定表明,USP30 的去泛素化催化活性有助于 OSCC 的细胞活力和谷氨酰胺消耗。随后,USP30 抑制剂 MF-094 被装载到 ZIF-8-PDA 和 PEGTK 中,以制备 ZIF-8-PDA-PEGTK 纳米颗粒,无论是在体外还是体内,都对 OSCC 的细胞活力和谷氨酰胺消耗具有出色的抑制作用。
结果表明 USP30 的临床意义,并表明纳米复合材料为治疗 OSCC 提供了靶向药物递送系统。