Takagi Tsuyoshi, Kin Shuichi, Nakase Yuen, Fukuda Kenichirou, Han Longhai, Ito Tadao, Fujiyama Jyunshin, Shimomura Katsumi, Sakakura Chouhei, Otsuji Eigo, Hagiwara Akeo, Yamagishi Hisakazu
Dept. of Digestive Surgery, Kyoto Prefectural University of Medicine.
Gan To Kagaku Ryoho. 2002 Nov;29(12):2318-21.
Peritoneal recurrence is one of the critical problems that occurs after surgery for gastrointestinal cancers. Since no curative treatment has been established for peritoneal recurrence, many efforts have been made to develop an effective method for preventing such recurrence. We focused on dextran sulfate, an anti-cell-adherence agent, to prevent peritoneal metastasis. Our previous studies in vitro and in vivo clarified that dextran sulfate prevents cancer cells from adhering to plastic flasks and the abdominal wall. In this study, we investigated the effects of dextran sulfate on cancer cells from the viewpoint of the cell cycle. Changes in gene expression caused by dextran sulfate were analyzed by cDNA microarrays. Analysis by cDNA microarray revealed the decreased expression of the genes essential to the progression of G1 and S phases. Our results indicate that dextran sulfate suppresses progression of the cell cycle as well as cell adhesion, suggesting that dextran sulfate could be used as an antimetastatic agent. Anti-cell-adherence agents with such mechanisms of action could be effective drugs for treatment during and after operation to prevent peritoneal metastases induced by surgical operation.
腹膜复发是胃肠道癌手术后出现的关键问题之一。由于尚未确立针对腹膜复发的根治性治疗方法，人们已做出诸多努力来开发预防此类复发的有效方法。我们聚焦于硫酸葡聚糖，一种抗细胞黏附剂，以预防腹膜转移。我们之前的体外和体内研究表明，硫酸葡聚糖可防止癌细胞黏附于塑料培养瓶和腹壁。在本研究中，我们从细胞周期的角度研究了硫酸葡聚糖对癌细胞的影响。通过cDNA微阵列分析了硫酸葡聚糖引起的基因表达变化。cDNA微阵列分析显示，G1期和S期进展所必需的基因表达下降。我们的结果表明，硫酸葡聚糖可抑制细胞周期进展以及细胞黏附，这表明硫酸葡聚糖可作为一种抗转移剂。具有此类作用机制的抗细胞黏附剂可能是手术期间及术后预防手术诱导腹膜转移的有效治疗药物。
