The Studies Of Regulating Effects Of Nitric Oxide Donor On Tumor Growth And Metastasis

Many studies have confirmed that nitric oxide (NO), as a small active molecule, participates in a variety of biological processes ranging from critical physiological functions to the pathophysiology of many diseases. NO acts as both signaling molecule and free radical in biological system. Recent years, the modulation effects of NO on tumor proliferation have been studied extensively and the results indicated that NO possesses both promotion and suppression effects on tumor. The goal of these studies is exploring the inhibitory effects of NO donors on tumor proliferation and metastasis by using cell culture and animal model. The mechanism was also studied by related gene expression and protein expression profile changing, are investigated. The mechanism of NO regulating tumor metastasis is further studied, as well as potential anti-tumor metastasis activities of NO donor. To used the contravesion properties of genotoxic and angiogenic of NO. In this study,1 Regulation of Proliferation inhibition on tumor Cell by Some Drugs influences the Nitric Oxide LevelDifferent concentrations of the drugs, including L-arginine(L-Arg), glyceryl trinitrate(GTN) and aminoguanidine(AG), were added to Lewis Lung Carcinoma cell culture medium. It was found that all three drugs inhibited the cell proliferation in high concentrations and reduced inhibition of cell proliferation with concentration decreasing. As a result, cell proliferation was promoted in low concentration of L-Arg or GTN; NO₂^-level increased in L-Arg and AG treatment groups with concentration reducing, but there was a positive correlation between NO₂^- level and GTN concentration. In tests of regulations of drug-combination, there was anantagonistic joint action between L-Arg and AG treatment in certain concentrations, and had a synergistic joint action between GTN and AG treatment mostly.2 Regulation of GTN on genes related to metastasis and protein expression profile of tumor cellsHela cells treated with 40 μ g/ml GTN showed inhibition of the growth activity. Microarray test involved in angiogenesis and tumor metastasis showed that the gene expressions profiles changed greatly. Most of the genes were down-regulated, which were more obvious than genes up-regulated. In two-dimensional gel electrophoresis test, a few protein spots were changed obviously and some flew different expression spots were picked up. MMP-9 and TIMP-1 gene expressions were examined with RT-PCR. ELISA assay was applied to determine the protein concentrations of MMP-9 and TIMP-1 in culture medium. The expression of MMP-9 in GTN group was greatly lower than that in control group, but the expression of TIMP-1 was not obviously changed. MMP-9 concentration in culture medium reduced dramatically but TIMP-1 did not. And the ratio of MMP-9/TIMP-1 was altered statistically.3 GTN in high concentration inhibiting the tumor metastasis and concerned with regulating the expression of MMP-9/TIMP-1In the model of IXC-bearing C57BL/6 mice, GTN taken orally at the concentration of 1.6g/L in 40 days could inhibit the tumor metastasis. The inhibition ratio of tumor metastasis was 52% and significantly different with control group. While the MMP-9 expression was dramatically lower than that in Control group, the TIMP-1 expression was not different in each group. The production balance of MMP-9 and TIMP-1 was changed. Mice in GTN-treatment groups showed no obviously affected by the drug to bodies or weights, nor the life style.In conclusion, the series studies showed that NO could regulate tumor...