Abnormal blood vessels formed by human liver cavernous hemangioma endothelial cells in nude mice are suitable for drug evaluation.
Cavernous hemangioma is vascular malformation with developmental aberrations. It was assumed that the abnormality of endothelial cells contributed greatly to the occurrence of cavernous hemangioma. In our previous study, we have found distinct characteristics of endothelial cells derived from human liver cavernous hemangioma (HCHEC). Here, we reported the abnormal vascular vessels formed by primary HCHEC in nude mice and that the drug podophyllotoxin can destroy HCHEC in vitro and in vivo. HCHEC was isolated from a human liver cavernous hemangioma specimen, and the HCHEC generated a red hemangioma-like mass 7 days after subcutaneously co-inoculating HCHEC and human liver cancer cells (Bel-7402) in nude mice. Lentiviral expression of GFP and immunohistochemistry for human CD31 was used to confirm that the HCHEC formed the blood vessels in nude mice. And the pathological features of vascular vessels formed by HCHEC were very similar to clinical cavernous hemangioma. In addition, by MTT assay, the drug podophyllotoxin was found inhibiting HCHEC viability, and by TUNEL and DNA ladder assays, podophyllotoxin was found inducing apoptosis of HCHEC. Moreover, podophyllotoxin was also effective for destroying the abnormal vascular vessels in the hemangioma-like mass in nude mice. In summary, the HCHEC can form abnormal blood vessels in nude mice, and we can evaluate drugs for cavernous hemangioma by using HCHEC in vitro and in vivo.
Zhang
Wen-jian
WJ
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, PR China.
Wu
Lian-qiu
LQ
Liu
Hong-lin
HL
Ye
Li-ya
LY
Xin
Yu-ling
YL
Grau
Georges E
GE
Lou
Jin-ning
JN
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006392:Hemangioma, Cavernous / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011034:Podophyllotoxin / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D011034:Podophyllotoxin