Endostar, a recombined humanized endostatin, inhibits lymphangiogenesis and lymphatic metastasis of Lewis lung carcinoma xenograft in mice

Abstract

Objective: The aim of this study was to investigate the effects of Endostar, a recombined humanized endostatin, on lymphatic tumor growth, lymphangiogenesis and lymphatic metastasis of Lewis lung carcinoma (LLC) xenograft in mice.

Methods: Lewis lung carcinoma xenografts were established in C57BL/6 mice by intravenous injection of 1 × 10(6) cells. Then the mice were assigned to two groups: the control group received caudal vein injections of 0.2 ml of 0.9% sodium chloride for 15 days, and the treatment group received 500 µg Endostar daily. Six weeks after LLC cell injection, the mice were sacrificed, and tumor multiplicity and tumor sizes were recorded. The expression of vascular endothelial growth factor C (VEGF-C) and podoplanin were observed by immunohistochemical staining.

Results: Tumor numbers and sizes in the control group were significantly higher than those of the treatment group. The microlymphatic vessel density (MLVD) was 5.67 ± 1.57 in the treatment group, which was markedly lower than in the control mice (7.78 ± 1.56). Two lymph node metastases were observed in the treatment group, and eight in the control group. Lymphatic metastases were more frequent in the control group than in the treatment group. Expression of VEGF-C in the control group was significantly higher than that in the treatment group.

Conclusion: Endostar significantly inhibits the lymphatic tumor growth, lymphangiogenesis and lymphatic metastasis of Lewis lung carcinoma xenografts, and its inhibitory effect is due to its ability to partially regulate the tumor expression of VEGF-C.