Objective:To investigate the activity of anti-malarial dihydroartemisinin （DHA） on tumor growth

lymphangiogenesis

nodal and lung metastasis and survival in mice bearing Lewis lung carcimoma （LLC）. Methods: The models of C57BL/6 mice transplantation tumors were established via subcutaneous injection of LLC cells and divided into 4 groups: control group

DHA group

DHA+ferrous sulfate （FS） group and FS group

with 25 mice in each group. Tumor volumes and weights

nodal and lung metastasis

and survival were monitored. Tumor lymphatic microvessel density （LMVD） was determined by lymphatic vessel endothelial hyaluronan receptor-1 （LYVE-1） immnohistochemistry. After LLC cells were treated with DHA or DHA+FS

protein and mRNA levels of vascular endothelial growth factor （VEGF） -C were evaluated by Western blotting and real time quantitative RT-PCR

respectively. Results: Oral administration of DHA or DHA+FS inhibited lymph node and lung metastasis

and prolonged survival. However

no significant tumor growth retardation effect was observed when mice were treated with DHA alone. The inhibited tumor metastasis was related to the decreased LMVD in the peritumoral regions

but not in the intratumoral regions. DHA significantly down-regulated the expression of VEGF-C protein and mRNA in LLC cells. Conclusion: DHA effectively inhibits LLC transplantation tumor lymphangiogenesis

nodal and lung metastasis

and may be a promising chemotherapeutic agent for controlling lung cancer metastasis by decreasing VEGF-C expression.