Artemisinin inhibits tumor lymphangiogenesis by suppression of vascular endothelial growth factor C.
We have previously reported that dihydroartemisinin is found to have a potent ability in influencing lymphatic endothelial cell migration and tube formation. In this study, we investigated the effect of artemisinin on tumor growth, lymphangiogenesis, metastasis and survival in mouse Lewis lung carcinoma (LLC) models. We found that orally administered artemisinin inhibited lymph node and lung metastasis and prolonged survival without retarding tumor growth. Consistent with the decrease in lymph node metastasis, tumor lymphangiogenesis and expression of vascular endothelial growth factor C (VEGF-C) was significantly decreased in artemisinin-treated mice, as compared to control mice. Furthermore, IL-1beta-induced p38 mitogen-activated protein kinase (MAPK) activation and upregulation of VEGF-C mRNA and protein in LLC cells was also suppressed by artemisinin or by the p38 MAPK inhibitor SB-203580, suggesting that p38 MAPK could serve as a mediator of proinflammatory cytokine-induced VEGF-C expression. These data indicate that artemisinin may be useful for the prevention of lymph node metastasis by downregulating VEGF-C and reducing tumor lymphangiogenesis.
Wang
Jun
J
Cancer Institute of People's Liberation Army, Xinqiao Hospital, Third Military Medical University, Chongqing, PR China.
Zhang
Bicheng
B
Guo
Yan
Y
Li
Guanghui
G
Xie
Qichao
Q
Zhu
Bo
B
Gao
Jianfei
J
Chen
Zhengtang
Z
D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D042583:Lymphangiogenesis / Q000187:drug effects; D008207:Lymphatic Metastasis / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control; D015996:Survival Rate; D042582:Vascular Endothelial Growth Factor C / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D037621:Artemisinins; D042582:Vascular Endothelial Growth Factor C; C031327:artemisinin; D048051:p38 Mitogen-Activated Protein Kinases