Effect of dihydroartemisinin and gasdermin E on the proliferation, migration, and pyroptosis of laryngeal cancer cells
10.3760/cma.j.cn115355-20231229-00261
- VernacularTitle:双氢青蒿素、焦孔素E对喉癌细胞增殖、转移及焦亡的影响
- Author:
Lingshuang JIN
1
;
Huina GUO
;
Li YANG
;
Zehui GAO
;
Shengyong JIN
;
Jing WANG
Author Information
1. 山西省肿瘤医院 中国医学科学院肿瘤医院山西医院 山西医科大学附属肿瘤医院头颈外科，太原 030013
- Keywords:
Laryngeal neoplasms;
Artemisinins;
Hexokinase;
Gasdermin E
- From:
Cancer Research and Clinic
2024;36(8):615-621
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of dihydroartemisinin (DHA) and gasdermin E(GSDME) on the proliferation, metastasis and pyroptosis of laryngeal cancer cells as well as its related mechanisms.Methods:Human laryngeal squamous cell cancer Hep-2 cells were taken and divided into 4 groups: the blank group (untreated Hep-2 cells), DHA group (Hep-2 cells treated with 50 μmol/L DHA), GSDME-siRNA group (Hep-2 cells transfected with GSDME-siRNA), and DHA+GSDME-siRNA group (Hep-2 cells treated with 50 μmol/L DHA and transfected with GSDME-siRNA). Methyl thiazolyl tetrazolium (MTT) method was used to detect the effect of DHA on the proliferation ability of Hep-2 cells, and the cell proliferation inhibition rate and half inhibitory concentration ( IC50) were calculated. Flow cytometry was used to detect the pyroptosis rate, Transwell assay was used to detect cell invasion ability and Western blot was used to detect the relative expression levels of GSDME, caspase-3, hexokinase Ⅱ (HK-Ⅱ), cyclophilin D, and voltage-dependent anion channel (VDAC) proteins. Results:The cell proliferation inhibition rates of Hep-2 cells treated with 10, 20, 40, 80, 160 μmol/L DHA for 48 h were higher than those treated with the corresponding concentration for 24 h (all P < 0.05). The IC50 values of Hep-2 cells treated by DHA for 24 h and 48 h were 57.20 μmol/L and 43.50 μmol/L, respectively, and thus 50 μmol/L DHA was selected for subsequent experiments. The pyroptosis rate was (6.5±0.8)%, (22.7±2.5)%, (3.1±0.6)% and (7.0±1.0)%, respectively in the blank group, DHA group, GSDME-siRNA group, and DHA+GSDME-siRNA group, and the difference was statistically significant ( F = 221.20, P < 0.05). The number of invasive cells was (153±14), (95±10), (205±16), and (148±16), respectively in the blank group, DHA group, GSDME-siRNA group, and DHA+GSDME-siRNA group, and the difference was statistically significant ( F = 56.89, P < 0.05). The results of Western blot showed that the relative expression levels of GSDME and caspase-3 in DHA group were higher than those in the blank group (both P < 0.05); the relative expression levels of GSDME and caspase-3 in GSDME-siRNA group were lower than those in DHA group (both P < 0.05); the relative expression levels of GSDME and caspase-3 in DHA+GSDME-siRNA group were higher than those in GSDME-siRNA group (both P < 0.05); the relative expression levels of HK-Ⅱ, cyclophilin D, and VDAC in DHA group were lower than those in the blank group (all P < 0.05); the relative expression levels of HK-Ⅱ, cyclophilin D, and VDAC in GSDME-siRNA group were higher than those in DHA group (all P < 0.05); the relative expression levels of HK-Ⅱ, cyclophilin D, and VDAC in DHA+GSDME-siRNA group were lower than those in GSDME-siRNA group (all P < 0.05). Conclusions:Dihydroartemisinin can increase the pyroptosis of laryngeal cancer cells and reduce cell proliferation and metastasis ability. The mechanism may be related to the inhibition of mitochondrial HK-Ⅱ expression.
