Carcinogenesis, Teratogenesis & Mutagenesis

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Inhibitory effect of FOLFOX4 combined with 1-MT on subcutaneous xenografts of gastric cancer in mice

LI Zhe-ping,LIU Xiao-li,WU Xi-run,SHEN Hui-qin,KANG Gui-yun,WANG Qi*   

  1. The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China
  • Received:2013-02-27 Revised:2013-05-18 Online:2013-07-30 Published:2013-07-30
  • Contact: WANG Qi,E-mail:wangqiqi72000@163.com

Abstract:

OBJECTIVE: To observe the inhibitory effect of FOLFOX4 combined with 1-MT on subcutaneous xenografts of gastric cancer in mice,and its influence on the expression of indoleamine-2,3-dioxygenase (IDO) in gastric cancer tissue. METHODS:Transfect the IDO eukaryotic expression plasmids (pcDNA3.1-IDO) into mice gastric cancer cell line MFC. The cell line expressing IDO stably was established. Expression of IDO was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Suspension of the MFC cells transfected with pcDNA3.1-IDO plasmid were inoculated subcutaneously in mice. Mice gastric carcinoma subcutaneous xenografts model expressing IDO highly was established (n=32). Blank control (n=8,untransfected MFC cells) and negative control (n=8,transfected MFC cells) were set up. The 32 model mice were randomly divided into 1-MT treatment group, FOLFOX4 treatment group,FOLFOX4+1-MT combined treatment(saline) group and non-treatment group (positive control group). There were eight mice in each group. The general condition of the mice and the differences in tumor quality were observed. Twelve day after cell suspension injection,all of the mice were sacrificed. The tumors were excised and weighed. Average tumor size and the tumor inhibitory rates of each group were calculated. The expression of IDO in gastric carcinoma tissues was evaluated by immunohistochemistry. RESULTS:Tumor of mice gastric carcinoma subcutaneous xenografts model expressing IDO highly was greater than blank control and negative control groups (P<0.05) and the expression of IDO in gastric carcinoma tissue was also increased significantly (P<0.05). After given 1-MT,FOLFOX4 and FOLFOX4+1-MT treatments,the food intake of model mice increased to varying degrees,more agile than before,and lethargy was also improved to different extents. The symptoms of FOLFOX4+1-MT combined treatment group were basically resolved. The tumors of 1-MT treatment,FOLFOX4 treatment and FOLFOX4+1-MT combined treatment group were smaller than no treatment group (P<0.05). The tumour inhibitory rates were 8.91%,80.20%,86.13%,respectively. FOLFOX4+1-MT combined treatment group tumor was less than 1-MT treatment group and FOLFOX4 treatment groups (P<0.05). The expressions of IDO in gastric carcinoma tissue of 1-MT treatment,FOLFOX4 treatment and FOLFOX+1-MT combined groups were lower than non-treatment group (P<0.05). The expression of IDO in gastric cancer tissue of FOLFOX4+1-MT combined treatment group was lower than 1-MT treatment group and FOLFOX4 treatment groups (P<0.05). CONCLUSION: 1-MT could inhibit the growth of subcutaneous xenografts of gastric carcinoma and the expression of IDO in gastric carcinoma tissue in mice. It could play synergistic antitumor role together with FOLFOX4.

Key words: FOLFOX4, 1-methyl tryptophan, indoleamine-2, 3-dioxygenase, gastric cancer