Abstract: Objective　To study the effect of NK4 overexpression mediated by intratumoral injection of lentivirus on the growth, invasion, metastasis and microangiogenesis of lung adenocarcinoma xenografts in nude mice. Methods　A549 cells were implanted into the right flank of BALB/c mice. After modeling, the mice were randomly divided into three groups: the PBS group, the LV-con group and the LV-NK4 group, 5 mice in each group. Mice in the three groups were received intratumoral injections of PBS (25 µL), LV-con (25 μL, 6×108 TU/mL) and LV-NK4 (25 μL, 6×108 TU/mL) respectively, twice at an interval of 3 days. The tumor volumes and weights of xenografts were measured, and the inhibitory rate of tumor was calculated at the end of the experiments. The tumor tissues and lung tissues in each group were observed by hematoxylin-eosin staining. The expressions of c-Met and CD31 were detected by immunohistochemistry, and microvessel density (MVD) was used to detect angiogenesis. The apoptosis of tumor cells in each group was detected by TUNEL. The expression levels of NK4 mRNA and protein in xenograft tumors were detected by real-time PCR and Western blot assay, respectively. Results　The xenograft tumor model of human lung adenocarcinoma was established successfully. The volume of tumor was smaller in the LV-NK4 group than that of the LV-con group and the PBS group (P＜0.05). There was no significant difference between the LV-con group and the PBS group. The tumor weight was significantly decreased in the LV-NK4 group compared with the LV-con group and the PBS group (P＜0.05). The tumour suppression rate was 44.51% in the LV-NK4 group and 10.35% in the LV-con group. The necrosis and apoptosis in tumor tissue of nude mice were significantly more in the LV-NK4 group than those in the LV-con group and the PBS group. The expression of c-Met in tumor tissue was significantly decreased in the LV-NK4 group, and the microangiogenesis was inhibited. There were no obvious lung metastases in the LV-NK4 group while there were obvious metastases in the LV-con group and the PBS group. The expression levels of NK4 mRNA and protein were significantly up-regulated in the LV-NK4 group than those of the other two groups. Conclusion　Lentivirus-mediated NK4 overexpression can inhibit the growth and lung metastasis of lung adenocarcinoma xenograft in nude mice by inhibiting the expression of c-Met protein and the formation of microvessels.

Key words: A549 cells, lung neoplasms, adenocarcinoma, neoplasm transplantation, lentivirus, genetic vectors, hepatocyte growth factor, NK4