ABSTRACT
<p><b>OBJECTIVE</b>To observe the inhibitory effect of citrus extract nobiletin on K562 cells xenograft in nude mice and discuss its anticancer activity and mechanism.</p><p><b>METHOD</b>The model of K562 cells xenograft was established in nude mice. Twenty-five nude mice were divided to five groups. After 24 hrs of inoculation with K562 tumor cells subcutaneously, 1% CMC-Na in the nude mice of model control group, nobiletin (12.5, 25, 50 mg x kg(-1)) in the nude mice of nobiletin groups and CTX (20 mg x kg(-1)) in positive control group were administered once every day. The nude mice were killed at 18th day-point of administration. The inhibitory rate of nobiletin on tumor was calculated according to the measured tumor weight. Immunohistochemistry assay was used to determine the effect of nobiletin on VEGF expression and MVD, and CAM assay was used to detect the effect of nobiletin on vessel regeneration.</p><p><b>RESULT</b>Nobiletin have notable inhibition on K562 cells xenograft in nude mice comparing with model control group (P < 0.01), the inhibitory rate of nobiletin groups were 36% -58%. The results of immunohistochemical technology showed that the expression of VEGF in nobiletin groups decreased significantly comparing with the model control group (P < 0.05, P < 0.01, P < 0.01). Nobiletin could remarkably decrease the angiogenesis within tumor tissues. The expression of CD34 in nobiletin low dose group and high dose group was lower than that in model control group (P < 0.05, P < 0.01). The result of CAM indicated that 4 microg and 2 microg nobiletin could inhibit the new blood vessels of CAM (P < 0.01).</p><p><b>CONCLUSION</b>Nobiletin inhibited the tumor growth and angiogenesis by reducing the VEGF expression of K562 cells xenograft in nude mice.</p>
Subject(s)
Animals , Humans , Male , Mice , Angiogenesis Inhibitors , Pharmacology , Antineoplastic Agents , Pharmacology , Citrus , Chemistry , Disease Models, Animal , Flavones , Pharmacology , Gene Expression Regulation, Neoplastic , K562 Cells , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Neoplasms , Drug Therapy , Genetics , Metabolism , Transplantation, Heterologous , Vascular Endothelial Growth Factors , Genetics , MetabolismABSTRACT
Objective To observe the protective effect of rhein-arginine (RhA) on rats ankylenteron and to explore the anti-inflammatory mechanism. Methods Sixty male SD rats were randomly divided into 6 groups:normal control group,model group,dexamethasone group (in the dose of 10 mg?kg-1) and low-,medium-and high-dose RhA groups (in the dose of 7.5 mg?kg-1,15 mg?kg-1,30 mg?kg-1 respectively). Except that the normal control group,the rats in other groups were induced ankylenteron. Intraperitoneal injection of saline was administered to the rats in the normal control group and the model group,and dexamethasone group and RhA groups were given the corresponding drugs according to the experimental design. The treatment lasted 7 days. On the 8th day after surgery the blood samples of each group were collected. The levels of interleukin-1?(IL-1?),interleukin-4(IL-4)and tumor necrosis factor-?(TNF-a)were determined by enzyme linked immunosorbent assay. Grades of ntestinal adhesion were ranked by macroscopic observation. The adhesive tissues between cecum and abdominal wall were taken for pathological observation and the determination of hydroxyproline (Hyp) content. Results RhA significantly relieved the experimental intestinal adhesion,Obviously decreased the levels of IL-1?and TNF-?,and inhibited the hyperplasia of fibrous connective tissue. However,there was no significant impact on the level of IL-4. Conclusion RhA can effectively prevent the information of postoperative ankylenteron by inhibiting the expression of inflammatory cytokines and reducing the inflammatory response.
