FOLFOX4与1-D-甲基色氨酸联合治疗对荷胃癌小鼠调节性T细胞的影响

doi:10.3969/j.issn.1004-616x.2013.04.006

癌变·畸变·突变

FOLFOX4与1-D-甲基色氨酸联合治疗对荷胃癌小鼠调节性T细胞的影响

康贵云¹,李哲萍^1,刘晓丽²,武希润²,申慧琴²,王琦²，*

1. 山西医科大学研究生院，山西太原 030001；2. 山西医科大学第二医院消化科，山西太原 030001

收稿日期:2013-03-29 修回日期:2013-05-15 出版日期:2013-07-30 发布日期:2013-07-30
通讯作者: 王琦，E-mail：wangqiqi72000@163.com
作者简介:康贵云 (1984- )，女，河北省邢台市人，硕士研究生，研究方向：胃癌免疫治疗。E-mail：1254661914@ qq.com
基金资助:
山西省科技攻关资助项目 (200903110)

The effect of combining FOLFOX4 with 1-D-methyl tryptophan on regulatory T cells of gastric cancer-bearing mice

KANG Gui-yun¹，LI Zhe-ping¹，LIU Xiao-li²，WU Xi-run²，SHEN Hui-qin²，WANG Qi²，*

1. Graduate School, Shanxi Medical University, Taiyuan 030001, Shanxi; 2. Department of Gastroenterology, Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China

Received:2013-03-29 Revised:2013-05-15 Online:2013-07-30 Published:2013-07-30
Contact: WANG Qi，E-mail：wangqiqi72000@163.com

摘要/Abstract

摘要：

目的：研究FOLFOX4与1-D-甲基色氨酸 (1-D-methyl tryptophan，1-D-MT)联合应用是否有利于改善荷胃癌小鼠的免疫耐受状态。方法：用脂质体转染法，将pcDNA3.1-IDO质粒和pcDNA3.1 (+)空质粒稳定转染MFC细胞，并设未转染组；用RT-PCR和Western blot法检测未转染组、空质粒转染组和pcDNA3.1-IDO转染组IDO mRNA和蛋白的表达；然后建立荷胃癌小鼠皮下移植瘤模型，并设未转染组、空质粒转染组，IDO+生理盐水 (NS)组、FOLFOX4组、1-D-MT组和FOLFOX4+1-D-MT联合处理组，采用流式细胞术检测各组小鼠脾脏中Treg细胞数量变化；RT-PCR检测FOXP3 mRNA表达量变化。结果：IDO mRNA与蛋白表达在稳定转染pcDNA3.1-IDO质粒组细胞较未转染组、空质粒转染组表达量明显增加 (P<0.05)。IDO+NS组小鼠脾脏Treg细胞比例及FOXP3 mRNA含量较未转染组、空质粒组均明显增多 (P<0.05)。FOLFOX4+1-D-MT组和1-D-MT组与FOLFOX4组相比，Treg细胞比例及FOXP3 mRNA含量均明显降低 (P<0.05)，且联合治疗组较1-D-MT组降低更明显 (P<0.01)。结论：通过抑制Treg的增殖及降低FOXP3 mRNA表达，FOLFOX4与1-D-MT联合应用可降低机体免疫逃逸能力。

关键词: 1-D-甲基色氨酸, FOLFOX4, 胃癌, 调节性T细胞

Abstract:

OBJECTIVE: To investigate whether combining 1-D-MT with FOLFOX4 could be useful to improve the immune tolerance of gastric cancer- bearing mice. METHODS：By using the lipofectamineTM 2000，the eukaryotic expression plasmid pcDNA3.1-IDO and empty vector pcDNA3.1 (+) were transfected in a MFC cell line，setting a control group. The expression of IDO was detected by reverse transcription polymerase chain reaction (RT-PCR) and western blot. Animal model of gastric cancer- bearing mice were established to receive normal saline (NS)，FOLFOX4，1-D-MT and 1-D-MT+FOLFOX4 therapy. By using flow cytometry，Treg cell ratio change was analyzed and FOXP3 mRNA expression change was assessed by RT-PCR. RESULTS：The expression of IDO mRNA and protein in the group trancfected with pcDNA3.1-IDO was obviousely ligher than the MFC group and the empty vector group (P<0.05). Treg cell ratio and FOXP3 mRNA expression in the transfected IDO negative control group with NS therapy was higher than the MFC and the empty vector groups (P<0.05). The Treg ratio and FOXP3 mRNA in 1-D-MT+FOLFOX4 and 1-D-MT groups were less than in FOLFOX4 group (P<0.05)，with 1-D-MT+FOLFOX4 group more markedly than 1-D-MT group (P<0.05). CONCLUSION：Combining 1-D-MT with FOLFOX4 could reduce Treg cell ratio and FOXP3 expression，thus reducing the immune escape.

Key words: 1-D-methyl tryptophan, FOLFOX4, gastric cancer, regulatory T cell

康贵云,李哲萍,刘晓丽,武希润,申慧琴,王琦. FOLFOX4与1-D-甲基色氨酸联合治疗对荷胃癌小鼠调节性T细胞的影响[J]. 癌变·畸变·突变, doi: 10.3969/j.issn.1004-616x.2013.04.006.

KANG Gui-yun，LI Zhe-ping，LIU Xiao-li，WU Xi-run，SHEN Hui-qin，WANG Qi. The effect of combining FOLFOX4 with 1-D-methyl tryptophan on regulatory T cells of gastric cancer-bearing mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, doi: 10.3969/j.issn.1004-616x.2013.04.006.

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FOLFOX4与1-D-甲基色氨酸联合治疗对荷胃癌小鼠调节性T细胞的影响

The effect of combining FOLFOX4 with 1-D-methyl tryptophan on regulatory T cells of gastric cancer-bearing mice

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