|
Objective: To observe the 5 - lipoxygenase / cyclooxygenase-2 dual inhibitors darbufelone of tumor growth of human gastric cancer SGC7901 cells subcutaneously into nude mice, and to explore its mechanism of tumor proliferation, apoptosis and angiogenesis . Methods: The nude mice models of solid tumors, the random divided into darbufelone treatment group and the control group (n = 7), darbufelone treatment group was given darbufelone 45mg · kg -1 · d -1 , continuously fed 28d, the control group was given normal saline. Were observed on 7, 14, 21 and 28 d subcutaneous tumor growth and nude body weight changes, drawing the tumor growth curve. The end of the first 4W after the beginning of the experiment animals were sacrificed to measure tumor mass, volume inhibitory rate was calculated; such as liver, kidney, spleen, lung tumor tissue for pathological examination. Chemical S-ABC was detected by RT-PCR and immunohistochemical tumor tissue COX-2 ,5-LOX, PCNA, Bcl-2 and caspase-3 expression. Marked microvascular CD34 and microvessel density, by RT-PCR and Western blot analysis transplanted tumor tissue of MMP-9 and VEGF. Results: 1. Successfully established gastric cancer transplanted into nude mice model. 2 tumor volume: darbufelone tumor xenografts volume (558.28 ± 79.01) mm 3 , and the control group (1698.28 ± 364.16) mm 3 (P lt; 0.05) . Weight of 3.darbufelone group inhibition rate was 58.42%. Pathological examination showed darbufelone group tumor necrosis area compared with the control group increased significantly, but the two sets of liver, kidney, spleen, lung vital organs morphology observed no significant pathological changes. 5.RT-PCR and immunohistochemical detection the results show darbufelone group decline in COX-2 ,5-LOX, PCNA, Bc1-2 mRNA and protein expression levels of caspase-3 mRNA and protein expression increased (P lt; 0.05 ). 6. Darbufelone group microvessel density (MVD) (15.36 ± 0.30) was significantly lower than the control group (29.47 ± 0.63) (P lt; 0.05). RT-PCR and Western blot results showed that darbufelone tumor tissue VEGF and MMP-9 mRNA and protein expression levels were significantly lower than the expression level in the control group (P lt; 0.05) Conclusion: darbufelone can significantly inhibit the growth of gastric cancer cells in vivo, and its mechanism may be related to the following factors: darbufelone by inhibiting COX-2 ,5-LOX, PCNA, Bcl-2 the expression levels, the increase in caspase-3 level, thereby inhibiting tumor proliferation and induce apoptosis; inhibition of transplanted tumor microvascular down of VEGF and MMP-9 expression levels of anti-angiogenic role.
|