Eggstein S, Imdahl A, Kohler M, Waibel M, Farthmann E H
Chirurgische Universitätsklinik Freiburg, Abteilung Allgemeine Chirurgie und Poliklinik, Federal Republic of Germany.
J Cancer Res Clin Oncol. 1991;117(1):37-42. doi: 10.1007/BF01613194.
Polyamines are essential factors of cell growth and differentiation. Modulation of the cellular polyamine content by 2-difluoromethylornithine (DFMO) inhibiting ornithine decarboxylase (ODC), or by hormones inducing ODC, influences cell growth. Gastrin acts trophically on some colonic carcinomas and their growth is inhibited by gastrin receptor blockers. The mechanism of the trophic action of gastrin on colonic carcinomas is not known. In this study the effect of gastrin, gastrin receptor blockers, epidermal growth factor (EGF) and DFMO on growth and ODC activity of four human colon carcinoma cell lines (SW 403, SW 1116, LS 174 T and Lovo) was investigated. Growth and ODC activity of all cell lines were inhibited by DFMO. Growth of the SW 403 cell line was increased by gastrin and inhibited by the gastrin receptor blocker benzotrypte. The other cell lines did not respond to gastrin and the gastrin receptor blocker. In SW 403 cells ODC activity was increased by gastrin, and was also elevated after treatment with the gastrin receptor blocker. These in vitro results were confirmed by studies on tumours that developed from SW 403 cells in nude mice. Combination of benzotrypte and DFMO did not enhance the antiproliferative effect. EGF increased growth of SW 403 cells, but no induction of ODC activity was measured. LS 174 T cells were not stimulated by EGF. Medium replacement was the strongest stimulus of ODC activity in SW 403 cells already inducing ODC after 3 h. During cell culture ODC activity was high after seeding and decreased continuously with increasing cell density. These data suggest that gastrin induces ODC in gastrin-sensitive colonic carcinoma cells. DFMO appears to be a valuable antiproliferative agent in colonic carcinoma cells.
多胺是细胞生长和分化的必需因子。通过抑制鸟氨酸脱羧酶（ODC）的2-二氟甲基鸟氨酸（DFMO）或通过诱导ODC的激素来调节细胞内多胺含量会影响细胞生长。胃泌素对某些结肠癌具有营养作用，其生长会被胃泌素受体阻滞剂抑制。胃泌素对结肠癌的营养作用机制尚不清楚。在本研究中，研究了胃泌素、胃泌素受体阻滞剂、表皮生长因子（EGF）和DFMO对四种人结肠癌细胞系（SW 403、SW 1116、LS 174 T和Lovo）生长和ODC活性的影响。所有细胞系的生长和ODC活性均被DFMO抑制。胃泌素可增加SW 403细胞系的生长，而胃泌素受体阻滞剂苯并三嗪可抑制其生长。其他细胞系对胃泌素和胃泌素受体阻滞剂无反应。在SW 403细胞中，胃泌素可增加ODC活性，用胃泌素受体阻滞剂处理后ODC活性也会升高。这些体外实验结果在对裸鼠体内由SW 403细胞形成的肿瘤的研究中得到了证实。苯并三嗪和DFMO联合使用并未增强抗增殖作用。EGF可增加SW 403细胞的生长，但未检测到ODC活性的诱导。LS 174 T细胞未被EGF刺激。更换培养基是SW 403细胞中ODC活性最强的刺激因素，3小时后即可诱导ODC活性。在细胞培养过程中，接种后ODC活性较高，并随着细胞密度的增加而持续下降。这些数据表明胃泌素可在对胃泌素敏感的结肠癌细胞中诱导ODC。DFMO似乎是结肠癌细胞中有价值的抗增殖剂。
