AMG-102 inhibits proliferation and induces apoptosis of laryngeal squamous cell carcinoma cells by regulating c-Met/PI3K/Akt pathway

Feng CAO; Xin LYU; Kaifeng DONG; Cai FAN; Jianjun ZHANG; Kun CHEN; Yi ZHANG; Bojing MA; Chunli HOU; Cuihong ZHANG

白话标题: AMG-102通过调控c-Met/PI3K/Akt通路抑制喉鳞癌细胞增殖和诱导凋亡
作者: Feng CAO ¹ ; Xin LYU ² ; Kaifeng DONG ³ ; Cai FAN ⁴ ; Jianjun ZHANG ⁴ ; Kun CHEN ⁵ ; Yi ZHANG ⁴ ; Bojing MA ⁴ ; Chunli HOU ⁶ ; Cuihong ZHANG ⁴
作者信息

1. Department of Radiation Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
2. Medical Department, Central Hospital of Baixiang County, Xingtai 055450, China
3. Department of Otolaryngology, the First Hospital of Hebei Medical University, Shijiazhuang 050031, China
4. Department of Radiation Oncology, the 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang 050082, China
5. Department of Otolaryngology Head and Neck Surgery, the 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang 050082, China
6. Department of Oncology, the 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang 050082, China
出版类型:Journal Article
关键字: AMG-102; Laryngeal neoplasms; Carcinoma, squamous cell; Proliferation; Apoptosis; c-Met; PI3K/Akt
来源: Chinese Journal of Oncology 2020;42(2):99-104
国家China
语言:Chinese
摘要: Objective:To investigate the effects of c-Met inhibitor AMG-102 on the proliferation and apoptosis of laryngeal squamous carcinoma Hep-2 cells and the underlying mechanism.
Methods:Laryngeal squamous carcinoma cell line Hep-2 cells were treated with 2.5, 5 and 10 μmol/L AMG-102, respectively. The proliferation activities of Hep-2 cells were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT). The apoptotic rate of Hep-2 cells was detected by flow cytometry analysis and Hoechst staining. The mRNA expression levels of apoptosis-related genes were detected by real-time quantitative polymerase Chain reaction (RT-qPCR), and the protein expressions of c-Met/PI3K/AKT pathway were detected by western blot.
Results:Compared with the control group, the proliferation rates of Hep-2 cells treated with 2.5, 5 and 10 μmol/L AMG-102 for 24 hours were (89.8±1.1)%, (79.8±1.0)% and (69.1±1.2)%, respectively; for 48 hours were (76.8±2.0)%, (60.2±1.1)% and (49.8±1.2)%, respectively; for 72 hours were (50.1±2.0)%, (41.5±1.1)% and (33.6±1.0), respectively, with significant differences (all P<0.05). The apoptotic rates of Hep-2 cells treated with 2.5, 5 and 10 μmol/L AMG-102 for 48 hours were (16.09±1.53)%, (27.51±2.02)% and (36.57±1.42)%, respectively, which were significantly higher than (3.62±0.10) % in the control group (all P<0.05). After treated with 2.5, 5 and 10 μmol/L AMG-102 for 48 hours, the relative expression levels of Bcl-2 mRNA in Hep-2 cells were 0.58±0.13, 0.38±0.12 and 0.20±0.13, respectively; the relative protein expression of p-Met were 80.0±3.8, 50.6±4.2 and 28.5±1.3, respectively; the relative protein expression of p-PI3K were 87.1±0.9, 54.2±1.2 and 21.0±1.2, respectively; the relative protein expression of p-AKT were 98.7±5.6, 56.9±3.2 and 32.2±4.3, respectively; which were significantly lower than those in the control group (all P<0.05). The relative expression levels of Bax mRNA were 1.78±0.13, 2.37±0.14 and 3.05±0.13, respectively, and the relative expression levels of caspase-3 mRNA were 1.98±0.14, 2.47±0.14 and 3.15±0.13, respectively, which were significantly higher than those in the control group (all P<0.05).
Conclusion:c-Met inhibitor AMG-102 could inhibit the proliferation and induce apoptosis of laryngeal squamous carcinoma Hep-2 cells by regulating the c-Met/PI3K/Akt pathway.