Inhibition of Cilengitide on Tumor Growth of A Nude Mouse Model with Lung Adenocarcinoma Cell Line A549 and Its Mechanism

Objective To observe the inhibition of cilengitide on tumor growth in a nude mouse model with lung adenocarcinoma cell line A549 and to explore its possible mechanism, in addition, to observe the therapeutic effect of cilengitide combined with cisplatin. Methods A549 cells were inoculated subcutaneously into the hind flank region of nude mice to establish xenograft models. The nude mice were randomly divided into 6 groups, control group (sodium chloride), cisplatin alone group, cilengitide alone (100 μg/d) group, cilengitide alone (200 μg/d) group, cilengitide (100 μg/d) plus cisplatin group and cilengitide (200 μg/d) plus cisplatin group. The tumor growth was observed. The expression of integrin β3 and β5 were determined by Western blot, and the expression levels of osteopontin(OPN), phosphorylated extra-cellular signal-regulated protein kinase 1(p-ERK1), vascular endothelial growth factor(VEGF) mRNA and protein were detected by reverse transcription polymerase chain reaction(RT-PCR) and Western blot, respectively. After cultured in vitro with cilengitide, VEGF agonist basic fibroblast growth factor (bFGF), vascular endothelial growth factor inhibtor(SU5416), ERK1 agonist epidermal growth factor (EGF) and ERK inhibitor PD98059, the phosphorylated ratio of ERK1 and VEGF protein expression in A549 cells were detected. Results Compared with the control group, OPN mRNA and protein expression in cilengitide groups were not significantly changed, while the expression of p-ERK1, VEGF mRNA and protein were significantly decreased in cilengitide groups. Moreover, tumor growth and the expression of p-ERK1, VEGF mRNA and protein were significantly decreased in cilengitide plus cisplatin groups compared with those in cisplatin alone groups. Conclusion Cilengitide could inhibit the tumor growth and enhance the effect of cisplatin in a nude mouse model with lung adenocarcinoma cell line A549, which may be involved in inhibiting ERK1 activation and VEGF expression.