Knockdown of Frizzled 2 inhibits mouse tongue squamous carcinoma and enhances CTLA4 monoclonal antibody efficacy
10.13699/j.cnki.1001-6821.2024.16.012
- VernacularTitle:敲低卷曲跨膜受体蛋白2抑制小鼠舌鳞癌并增强CTLA4单抗疗效的研究
- Author:
Hui-Yu LIU
1
;
Xiao-Jiao SUN
;
Zhen-Ming LIU
;
Tian-Cheng LI
Author Information
1. 北京大学第一医院耳鼻咽喉头颈外科,北京 100034
- Keywords:
Frizzled 2;
cytotoxic T lymphocyte associated antigen 4;
tongue squamous carcinoma;
immune check point;
tumor treatment
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(16):2359-2362
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the function of Frizzled 2(FZD2)in mouse tongue squamous cell carcinoma and its effect on cytotoxic T lymphocyte-associated antigen 4(CTLA4)monoclonal antibody.Methods Cell experiment:SCCVII mouse tongue squamous cell carcinomq cells were divided into blank control group(transfected LV-kdCon)and experimental group(transfected LV-kdFZD2).Cell proliferation ability was detected by cell counting kit-8(CCK-8);migration ability was detected by Transwell cell assay;and angiogenesis ability was verified by human umbilical vein endothelial cells.Animal experiments:Female C3H/He mice were constructed with tumor bearing mice model.Mice were divided into control group[injected with phosphate buffer solution(PBS)],kdFZD group(inoculated with experimental cells and injected with an equal amount of PBS),αCTLA4 group(inoculated with blank control cells subcutaneously and injected with CTLA4 monoclonal antibody)and kdFZD+αCTLA group(inoculated with experimental cells subcutaneously and injected with CTLA4 monoclonal antibody).The mRNA expression of tumor tissue was detected by quantitative polymerase chain reaction(qPCR),and the tumor volume and mass were measured.Results The relative expression levels of FZD2 mRNA in the control group and the experimental group were 1.01±0.18 and 0.52±0.18;the cell migration numbers were 466.70±44.10 and 160.00±26.46;the number of branch nodes of human umbilical vein endothelial cells were 108.70±6.35 and 84.33±10.02;the total capillary length were(20 235±2 229)and(16 549±338)μm,respectively,with statistical significance(P＜0.05,P＜0.01).The tumor volumes of control group,kdFZD group,αCTLA4 group and kdFZD+αCTLA group were(449.50±114.80),(131.10±13.49),(83.62±26.47)and(2.45±0.91)mm3;the tumor weights were(0.78±0.11),(0.22±0.06),(0.13±0.02)and(0.03±0.01)g,respectively,and the differences were statistically significant(P＜0.001,P＜0.000 1).Conclusion FZD2 can be used as a potential therapeutic target for tongue squamous cell carcinoma and is expected to be a key molecule in the optimization of adjuvant immunotherapy for tongue squamous cell carcinoma.
