Inhibitory effect of arsenic trioxide on angiogenesis and expression of vascular endothelial growth factor in gastric cancer.
OBJECTIVE
To investigate the inhibitory effect of As(2)O(3) on angiogenesis of tumor and expression of vascular endothelial growth factor (VEGF) in tumor cells in vivo and in vitro.


METHODS
The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were randomly divided into three groups. As(2)O(3) was injected into the arsenic-treated groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected into the control group. Microvessel density (MVD) and expression of VEGF were detected with immunofluorescence laser confocal technology. Further expression of VEGF protein and VEGF mRNA was measured with Western bloting and fluorescence quantitative RT- PCR in SGC-7901 cells treated with As(2)O(3).


RESULTS
In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As(2)O(3) respectively, about 50% and 30% tumor growth inhibition were observed correspondingly (P<0.05, P<0.05). Decrease in MVD appeared in As(2)O(3)-treated tumors compared with control group (P<0.001, P<0.001). MVD in tumors was significantly lower in 5 mg/kg group than in 2.5 mg/kg group (P<0.01). The fluorescence intensity levels of VEGF in tumor cells were significantly lowered in the arsenic-treated groups (P<0.01, P<0.01). The fluorescence intensity level of VEGF in 5 mg/kg group was lower than that in 2.5 mg/kg group (P<0.01). In vitro, the expression of VEGF protein decreased in dose- and time-dependent manner after the treatment with As(2)O(3), but in VEGF mRNA no significant difference was found between the control group and the treated groups.


CONCLUSIONS
As(2)O(3) can inhibit solid tumor growth by inhibiting the formation of new blood vessels. One of the mechanisms is that As(2)O(3) can inhibit VEGF protein expression.
Xiao
Yan-Feng
YF
Department of Pediatrics, the Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China. xiaoyanfeng0639@sina.com
Liu
Shan-Xi
SX
Wu
De-Dong
DD
Chen
Xi
X
Ren
Li-Fen
LF
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000077237:Arsenic Trioxide