Effects of endogenous nitric oxide induced by 5-fluorouracil and L-Arg on liver carcinoma in nude mice

Abstract

density of iNOS, iNOS activity and NO concentration are 31.693, 21.949, and 33.909, respectively, P < 0.05. The concentration of NO was related to the expression of P16 and BAX. The correlation coefficient was 0.764 and 0.554. CONCLUSION:5-FU combined with L-Arg can inhibit the growth of tumor in nude mice. The effect may be related to inducing the synthesis and increasing the activity of iNOS. The production of NO is increased, and it can enhance the expression of apoptosis-related gene and antioncogene. INTRODUCTIONOver the past decade or so, it has become evident that free radical gas nitric oxide acts as a novel transcellular messenger molecule in many key physiological and pathological processes. It appears that high levels of nitric oxide (NO) may be cytostatic or cytotoxic for tumor cells [1,2] . NO is a small gaseous molecule generated in a wide variety of cells as a product of the conversion of L-arginine into L-citrulline by the enzyme nitric oxide synthase (NOS). There have been few reports about the antitumor effects of endogenous nitric oxide in vivo [3,4] . In this study, we observed the inductive effects of 5-fluorouracil (5-FU) and L-arginine (L-Arg) on the endogenous nitic oxide in the human live carcinoma model in nude mice and proved the antitumor effects of the endogenous nitric oxide in the primary hepatic carcinoma and found effective adjuvant for 5-FU. The necrotic range and apoptosis index were significantly increased after the drug injection. The necrotic range was biggest in 5-FU + L-Arg group (χ 2 = 15.963, P < 0.05). MATERIALS AND METHODS MaterialsThe apoptosis indexes were as follows: NS, 17.4% ± 6.19%; 5-FU, 31.3% ± 12.3%; and 5-FU + L-Arg, 46%± 15.24% (P < 0.05, 5-FU vs 5-FU + L-Arg; P < 0.05, NS vs 5-FU + L-Arg; P < 0.05, NS vs 5-FU). The expression and activity of iNOS were increased in the tumor tissue.

Elevated nitric oxide levels associated with hepatic cell apoptosis during liver injury

“…It was reported that in osteopontin‐deficient (OPN (−/−)) hepatocytes, the downregulation of osteopontin enhanced the expression of iNOS, with a significant decrease of Bcl2 expression and death of liver cells . In addition, several experiments have shown that berberine combined with gamma irradiation, 5‐fluorouracil, and L‐arginine, can increase the NO level in liver cells, accompanied by increased Bax and the imbalance of Bax/Bcl‐2, leading to apoptosis of liver cells.…”

Gliclazide Prevents 5-FU-Induced Oral Mucositis by Reducing Oxidative Stress, Inflammation, and P-Selectin Adhesion Molecules

“…Excessive production of nitric oxide (NO) in inflammatory processes alters microvascular permeability and plays a pro-inflammatory role (Hatakeyama et al, 2006; Sanchez et al, 2008; Zhou and He, 2011). 5-FU can induce the expression of inducible nitric oxide synthase (iNOS) (Yin et al, 2007). Studies indicate that iNOS reduction by the therapeutic approach or the overexpression of caveolin-1 increases endothelial cell adhesiveness and the interaction of endothelial cell with leukocytes (Fernandez-Hernando et al, 2009, 2010; Atochin and Huang, 2010).…”

Effects of Shengjiang (Zingiberis Rhizoma Recens) and Its Processed Products on Nitric Oxide Production in Macrophage RAW 264.7 Cells

“…Modern pharmacological studies have found that a high concentration of NO mainly has a cytotoxic effect and inhibits and kills tumor cells through mechanisms including mediating the activation of macrophages to achieve an antitumor effect. The results of the study in which chemotherapy with 5-fluorouracil (5-FU), together with supplementation of the NO precursor L-arginine (L-Arg), was administered to a nude mice model of human liver cancer revealed that 5-FU could induce an increase in the expression and activity of iNOS in vivo , and after combination with L-Arg 5-FU could significantly enhance the expression and activity of iNOS and significantly increase the concentration of NO in tumor tissues, suggesting that endogenous NO plays an important role in the in vivo antitumor effect of 5-FU combined with L-Arg [ 9 ].…”