Cox-2 inhibitors in combination with cisplatin for lung cancer research progress of angiogenesis

Abstract

Objective To investigate the selective cyclooxygenase-2 (COX-2) inhibitor nimesulide (NIM) and in combination with cisplatin (DDP) on A549 cells in nude mice transplanted tumor angiogenesis and its mechanism for the treatment oflung cancer in vivo. Methods Lung cancer A549 cells and established A549 lung xenografts in nude mice model.According to the method of random number table, the subjects were divided into four groups for drug intervention: control group, NIM group, DDP group, NIM+ DDP group, each group of 8, and the general state was observed.Mice were killed by cervical dislocation on 22nd days, then obtained tumor tissues, weighed tumor, measured tumor diameter and calculated tumor inhibition rate.To clarify the influence of nimesulide alone or in combination with cisplatin in A549 lung cancer xenograft tumor neovascularization, labeled microvessel with CD31 and counted microvessel density using microvessel counts.Immunohistochemistry was used to detect the expression of endovascular endothelial growth factor in lung cancer A549 in nude mice. Results In this study, a nude mouse model of lung cancer A549 was successfully constructed.The tumor volume of NIM+ DDP group increased more slowly than the other three groups on the 9th, 13th, 17th and 21st day (all P<0.001). Nim+ DDP group had the largest tumor inhibition rate.The microvessel density of NIM+ DDP group was lower than that of the other three groups (F=27.861, P<0.001). Conclusions The selective COX-2 inhibitors could inhibit angiogenesis, suggesting that selective COX-2 inhibitors have anti-tumor capabilities and may be used as a lung cancer targeted therapy.The selective COX-2 inhibitor combined with cisplatin had a more significant inhibitory effect on the expression of neovascularization factors and the growth of transplanted tumor in nude mice with lung cancer A549 cells. Key words: Lung neoplasms; Vascular endothelial growth factors; Inhibition of cyclooxygenase-2