Department of Oral and Maxillofacial Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan City, 433030, China.
Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Qiaokou District, Wuhan City, 433030, China.
Biosci Rep. 2020 Mar 27;40(3). doi: 10.1042/BSR20200079.
Oral squamous cell carcinoma (OSCC) is the most common malignancy in the oral cavity, which accounts for >90% of all diagnosed oral cancers. 2-phenylethynesulfonamide (PES) was known as a selective heat shock protein 70 (Hsp70) function inhibitor, which induced cytotoxic effects on various tumor cell types, but showed to be less toxic to normal cells. However, no associated evaluation of PES on OSCC was found. In the present study, the proliferation of OSCC cells treated with PES was analyzed using a CCK-8 assay. The effects of PES on the cell cycle and apoptosis of OSCC cells were determined by flow cytometric analyses. Expression of associated protein was determined by Western blot analysis. The results of the present study showed that PES inhibited the proliferation of OSCC cell lines in vivo and in vitro. PES induced apoptosis and arrested the cell cycle of OSCC cells. PES inhibited the expression of X-linked inhibitor of apoptosis protein (XIAP), baculoviral IAP repeat containing 2 (c-IAP1), phosphorylated AKT (p-AKT), and phosphorylated extracellular signal-regulated kinase (p-ERK). Additionally, knockdown of Hsp70 enhanced the effects of PES. By contrast, overexpression of Hsp70 attenuated the inhibitory effects of PES on cell viability. PES disrupted the interaction between Hsp70 and XIAP. In conclusion, the present study demonstrated that PES suppresses the growth of OSCC cells through Hsp70-dependent mechanism.
口腔鳞状细胞癌 (OSCC) 是口腔最常见的恶性肿瘤，占所有诊断为口腔癌的 90%以上。2-苯乙亚磺酰胺 (PES) 是一种已知的选择性热休克蛋白 70 (Hsp70) 功能抑制剂，对各种肿瘤细胞类型具有细胞毒性作用，但对正常细胞的毒性较小。然而，目前尚未发现 PES 对 OSCC 的相关评估。在本研究中，通过 CCK-8 测定分析了 PES 处理的 OSCC 细胞的增殖。通过流式细胞术分析确定 PES 对 OSCC 细胞周期和凋亡的影响。通过 Western blot 分析确定相关蛋白的表达。本研究结果表明，PES 抑制 OSCC 细胞系在体内和体外的增殖。PES 诱导 OSCC 细胞凋亡并阻滞细胞周期。PES 抑制 X 连锁凋亡抑制蛋白 (XIAP)、杆状病毒 IAP 重复包含 2 (c-IAP1)、磷酸化 AKT (p-AKT) 和磷酸化细胞外信号调节激酶 (p-ERK) 的表达。此外，Hsp70 的敲低增强了 PES 的作用。相反，Hsp70 的过表达减弱了 PES 对细胞活力的抑制作用。PES 破坏了 Hsp70 和 XIAP 之间的相互作用。综上所述，本研究表明 PES 通过 Hsp70 依赖性机制抑制 OSCC 细胞的生长。
