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Role of decoy receptor 3 and its tumor necrosis factor ligand-related molecular 1A in the treatment of pancreatic cancer implantation with CD 4 and CD 8 double negative T cells in nude mice

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Author:
No author available
Journal Title:
Chinese Journal of Pancreatology
Issue:
1
DOI:
10.3760/cma.j.cn115667-20200706-00105
Key Word:
胰腺肿瘤;T淋巴细胞;诱饵受体3;肿瘤坏死因子配体相关分子1A;Pancreatic neoplasms;T lymphocytes;Decoy receptor 3;Tumor necrosis factor ligand-related molecule 1A

Abstract: Objective:To explore the role of decoy receptor 3(DcR3) and its ligand tumor necrosis factor ligand-related molecule 1A(TL1A) in the treatment of pancreatic cancer implanted tumors in nude mice with CD 4 and CD 8 double negative T cells (DNT cells). Methods:DNT cells derived from peripheral blood of healthy volunteers were cultured in vitro by antibody adsorption method. A nude mouse model of pancreatic cancer implantation was established and randomly divided into DNT cell treatment group (tail vein injection of 1×10 8/ml DNT cell suspension), gemcitabine treatment group (tail vein injection of 50 mg/kg gemcitabine) and control group (no treatment). The tumor volume and weight in each group were measured after 50 days. Western blotting and qRT-PCR were used to detect the protein and mRNA expression of DcR3 and TL1A in nude mice implanted tumor tissues in each group, and TUNEL method was used to detect the apoptosis rate of nude mice implanted tumors in each group. Results:The tumor volume of the DNT cell treatment group, gemcitabine treatment group, and control group was (670.28±124.54), (604.60±179.16), (1738.80±391.39)mm 3, and the tumor weight was (225.60±8.12), (222.69±8.73), (265.07±10.76)mg, and the volume and weight of implanted tumors in the DNT cell treatment group and gemcitabine treatment group were significantly lower than those in the control group, and the differences were statistically significant (all P values <0.001). The expression levels of DcR3 protein and mRNA in the DNT cell treatment group and gemcitabine treatment group (0.56±0.02, 3.74±0.19; 0.57±0.03, 3.40±0.39) were significantly higher than those in the control group (0.39±0.04, 0.92±0.05), while the expression levels of TL1A protein and mRNA (0.41±0.03, 0.83±0.11; 0.40±0.05, 0.79±0.08) were significantly lower than those of the control group (0.81±0.05, 1.70±0.36), and the differences were statistically significant (all P values <0.001). The apoptotic rate of implanted tumors in the DNT cell treatment group was (53.2±11.2)%, and that in the gemcitabine treatment group was (56.2±8.6)%, which were significantly higher than the control group (10.3±3.2)%, and the differences were statistically significant ( all P values <0.001). Conclusions:DNT cells had a significant inhibitory effect on the growth of pancreatic cancer implanted tumors in nude mice. DcR3-TL1A may be involved in the anti-tumor mechanism of DNT cells.

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