Downregulation of Tie2 gene by a novel antitumor sulfolipid, 3'-sulfoquinovosyl-1'-monoacylglycerol, targeting angiogenesis.
We previously reported that 3'-sulfoquinovosyl-1'-monoacylglycerol (SQMG) was effective in suppressing the growth of solid tumors due to hemorrhagic necrosis in vivo. In the present study, we investigated the antiangiogenic effect of SQMG. In vivo assessment of antitumor assays showed that some tumor cell lines, but not others, were sensitive to SQMG. Microscopic study suggested that in SQMG-sensitive tumors, but not SQMG-resistant tumors, angiogenesis was reduced. We next investigated gene expression relating to angiogenesis in tumor tissues by quantitative real-time polymerase chain reaction. Consequently, although vascular endothelial growth factor gene expression was not detected with significant differences among the cases, significant downregulation of Tie2 gene expression was observed in all SQMG-sensitive tumors as compared with controls, but not in SQMG-resistant tumors. These data suggested that the antitumor effects of SQMG could be attributed to antiangiogenic effects, possibly via the downregulation of Tie2 gene expression in SQMG-sensitive tumors.
Mori
Yoko
Y
Marine Biomedical Institute, Sapporo Medical University School of Medicine, S1, W17, Chuo-ku, Sapporo 060-8556, Japan.
Sahara
Hiroeki
H
Matsumoto
Kayo
K
Takahashi
Nobuaki
N
Yamazaki
Takayuki
T
Ohta
Keisuke
K
Aoki
Satoko
S
Miura
Masahiko
M
Sugawara
Fumio
F
Sakaguchi
Kengo
K
Sato
Noriyuki
N
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D006017:Glycolipids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D042787:Receptor, TIE-2 / Q000235:genetics* / Q000378:metabolism
C477365:1-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride; D020533:Angiogenesis Inhibitors; D006017:Glycolipids; D047428:Protein Kinase Inhibitors; D042787:Receptor, TIE-2