Harada Koji, Yoshida Hideo, Sato Mitsunobu
Second Department of Oral and Maxillofacial Surgery, University of Tokushima, School of Dentistry, Tokushima 770-8504, Japan.
Int J Oncol. 2005 Dec;27(6):1489-97.
Vesnarinone is a synthesized positive oral inotropic agent that has multiple biological activities on mammalian cells both in vitro and in vivo. This agent has been reported in relation to its antitumor effect with apoptosis-inducing activity. In the present study, we determined whether vesnarinone could suppress angiogenesis and growth of human oral squamous cell carcinoma cells in vitro and in vivo. Vesnarinone significantly inhibited the in vitro and in vivo expression of two major proangiogenic molecules, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), in cultured cells and in cells implanted into the subcutaneous tissue of nude mice. Also, vesnarinone inhibited the nuclear factor-kappa B (NF-kappaB) activity in human oral squamous cell carcinoma cells in vitro. The decreased expression of VEGF and IL-8 correlated with decreased tumorigenicity and decreased vascularization of lesions in vivo. These findings suggest that vesnarinone can suppress the angiogenesis and growth of oral squamous cell carcinoma cells by inhibiting the expression of VEGF and IL-8 involved in blockade of NF-kappaB activity.
维司那林是一种合成的口服正性肌力药物，在体外和体内对哺乳动物细胞均具有多种生物学活性。该药物已被报道具有诱导凋亡的抗肿瘤作用。在本研究中，我们确定维司那林是否能在体外和体内抑制人口腔鳞状细胞癌细胞的血管生成和生长。维司那林显著抑制了两种主要促血管生成分子，即血管内皮生长因子（VEGF）和白细胞介素-8（IL-8）在体外培养细胞和植入裸鼠皮下组织的细胞中的体内外表达。此外，维司那林在体外抑制了人口腔鳞状细胞癌细胞中的核因子-κB（NF-κB）活性。VEGF和IL-8表达的降低与体内肿瘤发生性降低和病变血管化减少相关。这些发现表明，维司那林可通过抑制参与阻断NF-κB活性的VEGF和IL-8的表达来抑制口腔鳞状细胞癌细胞的血管生成和生长。
