Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine; Shanghai Jiaotong University School of Medicine Ear Institute; Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, 200092, China.
Center for Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200031, China.
World J Surg Oncol. 2022 Aug 19;20(1):262. doi: 10.1186/s12957-022-02728-6.
The occurrence and development of malignancies include excessive proliferation and apoptosis resistance in tumor cells. This study aimed to identify the effects of Notch1 signaling on proliferation and apoptosis of laryngeal cancer cells in a hypoxic microenvironment.
Notch1 and Ki-67 expression in laryngeal squamous cell carcinoma (LSCC) tissues was detected by immunohistochemistry. The apoptotic index (AI) of LSCC was evaluated by the TUNEL method. Small interfering RNA (siRNA) was used to inhibit Notch1 expression in laryngeal cancer cells. Real-time PCR was used to measure Notch1, Hes1, and Hey1 mRNA expression, and Western blotting was used to measure Notch1 and Notch1 intracellular domain (N1ICD) protein expression. Annexin V-FITC/propidium iodide staining and Cell Counting Kit-8 assays were used to measure cell apoptosis and proliferation, respectively.
Notch1 expression was significantly related to the proliferation index (PI) and AI in LSCC tissues. Hypoxia could induce proliferation and inhibit apoptosis in cancer cells. Notch1 expression and Notch1 signaling activity could be upregulated by hypoxia. Suppressing Notch1 signaling activity in hypoxic cells could decrease proliferation and increase apoptosis.
Our study has demonstrated that hypoxia may promote proliferation and inhibit apoptosis of laryngeal cancer cells. Notch1 signaling may play a pivotal role in regulating the proliferation and apoptosis resistance of laryngeal cancer cells under hypoxic conditions.
恶性肿瘤的发生和发展包括肿瘤细胞的过度增殖和凋亡抵抗。本研究旨在探讨 Notch1 信号通路在低氧微环境下对喉癌细胞增殖和凋亡的影响。
采用免疫组化法检测喉鳞状细胞癌（LSCC）组织中 Notch1 和 Ki-67 的表达，TUNEL 法检测 LSCC 的凋亡指数（AI）。采用小干扰 RNA（siRNA）抑制喉癌细胞 Notch1 的表达。实时 PCR 检测 Notch1、Hes1 和 Hey1 mRNA 的表达，Western blot 检测 Notch1 和 Notch1 细胞内结构域（N1ICD）蛋白的表达。用 Annexin V-FITC/碘化丙啶染色和细胞计数试剂盒-8 检测细胞凋亡和增殖。
Notch1 表达与 LSCC 组织的增殖指数（PI）和 AI 显著相关。低氧可诱导癌细胞增殖并抑制凋亡。低氧可上调 Notch1 表达和 Notch1 信号活性。抑制低氧细胞中的 Notch1 信号活性可降低增殖并增加凋亡。
本研究表明，低氧可能促进喉癌细胞的增殖并抑制其凋亡。Notch1 信号通路可能在调节低氧条件下喉癌细胞的增殖和凋亡抵抗中发挥关键作用。
