Zheng Kai, Li Zexi, Ding Xu, Li Huaiqi
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215000 Jiangsu China.
Department of Oral and Maxillofacial Surgery, Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, NO.136 Hanzhong Road, Nanjing, 210029 Jiangsu China.
Cytotechnology. 2023 Feb;75(1):17-25. doi: 10.1007/s10616-022-00556-w. Epub 2022 Oct 28.
Oral squamous cell carcinoma (OSCC) is an epithelial malignant tumor with great challenges of tumor metastasis and drug resistance. Nutlin-3 is a MDM2 inhibitor that can potently activate tumor suppressor gene p53. However, the exact role of Nutlin-3 in OSCC has not been identified yet. SCC-9 cells were treated with 0, 2.5, 5, 10, 20 μM Nutlin3. MDM2 and p53 protein levels were assessed using western blot analysis. Then, CCK8 assay, clone formation assay, TUNEL staining, wound healing and transwell assays were conducted to analyze the influences of Nutlin3 on the proliferation, apoptosis, migration, and invasion in SCC-9 cells. Moreover, SCC-9 cells were co-treated with 0, 0.5, 1, 2.5, 5 μM cisplatin and Nutlin3 to determine the effect of Nutlin3 on cisplatin chemosensitivity in OSCC. As expected, Nutlin-3 inhibited MDM2 but restored p53 in OSCC in a concentration-dependent manner. Meanwhile, Nutlin-3 suppressed the proliferation, clone formation, migration, invasion and epithelial-mesenchymal transition of SCC-9 cells and both boosted the apoptosis. In addition, Nutlin-3 caused a reduced cell viability and an elevated cell apoptosis rate in cisplatin-treated SCC-9 cells, indicating that Nutlin-3 enhanced cisplatin chemosensitivity in OSCC cells. Taken together, Nutlin-3 may suppress tumorigenesis and progression of OSCC and enhance chemosensitivity to cisplatin in OSCC.
口腔鳞状细胞癌（OSCC）是一种上皮性恶性肿瘤，在肿瘤转移和耐药性方面面临巨大挑战。Nutlin-3是一种MDM2抑制剂，可有效激活肿瘤抑制基因p53。然而，Nutlin-3在OSCC中的确切作用尚未明确。用0、2.5、5、10、20μM的Nutlin3处理SCC-9细胞。采用蛋白质免疫印迹分析评估MDM2和p53蛋白水平。然后，进行CCK8检测、克隆形成检测、TUNEL染色、伤口愈合检测和Transwell检测，以分析Nutlin3对SCC-9细胞增殖、凋亡、迁移和侵袭的影响。此外，将SCC-9细胞与0、0.5、1、2.5、5μM顺铂和Nutlin3共同处理，以确定Nutlin3对OSCC中顺铂化疗敏感性的影响。正如预期的那样，Nutlin-3在OSCC中以浓度依赖性方式抑制MDM2但恢复p53。同时，Nutlin-3抑制SCC-9细胞的增殖、克隆形成、迁移、侵袭和上皮-间质转化，并促进凋亡。此外，Nutlin-3导致顺铂处理的SCC-9细胞的细胞活力降低和细胞凋亡率升高，表明Nutlin-3增强了OSCC细胞对顺铂的化疗敏感性。综上所述，Nutlin-3可能抑制OSCC的肿瘤发生和进展，并增强OSCC对顺铂的化疗敏感性。
