S-1 inhibits tumorigenicity and angiogenesis of human oral squamous cell carcinoma cells by suppressing expression of phosphorylated Akt, vascular endothelial growth factor and fibroblast growth factor-2.
It has been reported that S-1 can exert antitumor effects on various human cancers including oral squamous cell carcinoma (OSCC). However, little is known about the detailed mechanisms of the antitumor activity of S-1. In the present study, we determined whether S-1 could suppress the angiogenesis and growth of human OSCC cells in vitro and in vivo. The S-1 component (5-FU plus CDHP) significantly suppressed the growth and migration of OSCC cells and BAEC, which inhibited tubule formation in HUVECs in vitro. Also, S-1 inhibited the nuclear factor-kappaB (NF-kappaB) activity in human OSCC cells in vitro. Moreover, S-1 inhibited the expression of survival signal, phosphorylated Akt (p-Akt), and of two major proangiogenic molecules, vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2), in cells implanted into the subcutaneous tissue of nude mice. The decreased expression of p-Akt, VEGF and FGF-2 correlated with decreased tumorigenicity and decreased vascularization of lesions in vivo. These findings suggest that S-1 can suppress the angiogenesis and growth of OSCC cells by inhibiting the expression of p-Akt, VEGF and FGF-2 involved in the blockade of Akt/NF-kappaB pathway.
Harada
Koji
K
Therapeutic Regulation for Oral Tumor, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8504, Japan. harako@dent.tokushima-u.ac.jp
Supriatno
Kawashima
Yuichiro
Y
Yoshida
Hideo
H
Sato
Mitsunobu
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010094:Oxonic Acid / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D005641:Tegafur / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D051057:Proto-Oncogene Proteins c-akt