[Antiglioma activity of endothelial progenitor cells transduced with HSV-TK via inhibiting angiogenesis in vitro and in vivo].
OBJECTIVE
To investigate the potentiality of herpes simplex virus thymidine kinase transduced endothelial progenitor cells (EPC-TK) as angiogenesis-targeting vector in the glioma treatment in vitro and in vivo.


METHODS
EPC-TK were mixed with human umbilical vein endothelial cells (HUVECs), U87 or U251 cells at various ratios for ganciclovir (GCV) treatment. The bystander effect was observed by counting the survival cells using MTT assay, and the apoptotic cells were determined by annexin-V and propidium iodide (PI) staining. EPC-TK, EPCs, or phosphate buffered saline (PBS) were injected into the nude mice model of glioma xenograft by tail vein, for the EPC-TK group, EPC group, and PBS group, respectively. And then the changes of tumor volume and tumor vasculature were observed.


RESULTS
GCV killed most EPC-TK and reduced the number of other viable cells in a cell:cell ratio-dependent and time-dependent manner. EPC-TK obviously inhibited tumor growth. The tumor volumes on day 21 were 1741.20+/- 576.10 mm(3), 3275.52 +/- 710.86 mm(3) and 3033.09+/-1134.86 mm(3) in the EPC-TK, EPC and PBS group, respectively. EPC-TK also displayed a significant effect on the inhibition of tumor angiogenesis.


CONCLUSIONS
EPC-TK can exert a potent antiglioma effect via inhibiting angiogenesis.
Department of Neurosurgery, Nanjing Medical University, Nanjing, Jiangsu, 210029 People's Republic of China.
Jun-xia
JX
Zhang
Peng
P
Zhao
Rui
R
Li
Lei
L
Shi
Zi-hao
ZH
Cheng
Yong-ping
YP
You
Zhen
Z
Fu
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D024201:Bystander Effect; D002472:Cell Transformation, Viral / Q000502:physiology; D042783:Endothelial Cells / Q000821:virology; D004727:Endothelium; D005822:Genetic Vectors; D005910:Glioma / Q000628:therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000998:Antiviral Agents; D013937:Thymidine Kinase