The Antitumor Effect And Mechanisms Study Of Arsenic Trioxide On 615 Inbreeding Mice Experimental Gastric Cancer

Objective Gastric cancer is one of the most common malignant tumors in China. It lacks early detective and effective curing methods. AsA is effective to inhibit gastric cancer cell lines growth in vitro but sti 11 lacks in vivo till now. So our experiment is to develop mice implanting models of MFC (mouse forestomach carcinoma cell line), and observe its antitumor effect and the mechanisms of inducing apoptosis.Methods The tumor-bearing mice models were established in 615 mice by inoculating MFC 3X106 respectively into subcutaneous tissues . Forty mice were divided into 5 groups at random. NS, or 5-FU , or As2O3) of different concentrations was injected intraperitoneally respectively per day for 8 days, starting from 24 hours after the tumor inoculation. Observing the tumor growth per day , then killed them all on the 9th day to obtain the tumor inhibition rate(TIR) and histological changes in gastric tissues under microscope. Also we analyze tumor cell apoptosis by flow cytometry(FCM) and electron microscope, and the expression of apoptosis-related proteins Bcl-2, Bax by immunohistochemisty analyzing.Results 1. All mice successfully grew subcutaneous transplantation of MFC cells. 2. Significant inhibiting solid tumor growth effects were observed in the groups treated with As2O3 2mg. kg-1. d-1, the inhibitory rate is 59.49%. 3. Through microscope, mice treated with 4 mg. kg-1, d-1 As2O3 showed necrosis, while other groups seldom . 4. By the inspection of transmission electonic microscope, the groups treated with As2O3 and 5-FU all showed characteristics of apoptosis, such as apoptonic bodies and the macrophagical change. 5. The sub Gl peaks were observed by FCM on the As203 and 5-FU specimens, especially in the As2O3 of 2mg. kg-1. d-1 groups. 6. Expressions of Bcl-2 protein were down-regulated with the rise of theconcentration of As2O3, while Bax were up-regulated.Conclusions 1. As2O3 is effective in treating mice bearing gastric cancer by inducing apoptosis. 2. Its molecular mechanisms may be through downregulation of Bcl-2 expression and upregulation of Bax expression. 3. 2mg. kg-1. d-1 may be the appropriate concentration of As2O3 in its antitumor effect, and is better than 5~FU. 4. Large dose(4 mg. kg-1. d-1 ) of As2O3 may have cytotoxic effect. 5. As203 may be a new and effective medicine to treat gastric cancer. It deserves further research.Postgraduate Zhan Shujun (Oncology) Directed by Liang JunZhao Yuanyuan...