Mukaida H, Hirabayashi N, Hirai T, Yamashita Y, Iwata T, Saeki S, Toge T
Department of Surgery, Hiroshima University, Japan.
Surg Today. 1994;24(3):234-40. doi: 10.1007/BF02032894.
The growth interactions between human cancer cells and primary cultured human fibroblasts, and the effects of suramin on them, were investigated using a double-chamber technique combined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. Human fibroblasts obtained from various organs resected surgically were cultured in a monolayer and used after the third or fourth passage. In the double-chamber assay, the growth of cancer cells in the top chamber was significantly stimulated by some types of fibroblasts in the bottom chamber in a fibroblast density-dependent manner. Interestingly, the growth of cancer cells was stimulated at 140%-147% by fibroblasts obtained from an organ where cancer cells had developed, the MCF-7 versus mammary fibroblasts, and in LS-180 versus colonic fibroblasts, but not by their fibroblast-conditioned medium. Suramin completely inhibited the growth-enhancing interaction between MCF-7 and mammary fibroblasts, and between SH-101 and lung fibroblasts at a clinical concentration of from 50 micrograms/ml to 300 micrograms/ml. It also reduced the growth of LS-180 co-cultured with colon-fibroblasts, but the inhibitory effect was incomplete. These results suggest that mutual growth reliance exists between human cancer cells and primary cultured fibroblasts by diffusible factors secreted by both cells, and that these enhancing effects are related in part to the growth and metastasis of cancer cells in vivo. Suramin was found to have an inhibitory effect on their interaction at a clinically achievable concentration in vitro.
采用双室技术结合3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H溴化四氮唑(MTT) 法，研究了人癌细胞与原代培养的人成纤维细胞之间的生长相互作用以及苏拉明对它们的影响。从手术切除的各种器官中获取的人成纤维细胞进行单层培养，在传代3次或4次后使用。在双室试验中，上室癌细胞的生长受到下室某些类型成纤维细胞的显著刺激，且呈成纤维细胞密度依赖性。有趣的是，来自癌细胞已发生的器官的成纤维细胞（MCF-7与乳腺成纤维细胞，以及LS-180与结肠成纤维细胞）可将癌细胞的生长刺激140%-147%，但其条件培养基则无此作用。苏拉明在临床浓度50微克/毫升至300微克/毫升时，完全抑制了MCF-7与乳腺成纤维细胞以及SH-101与肺成纤维细胞之间的生长增强相互作用。它还降低了与结肠成纤维细胞共培养的LS-180的生长，但抑制作用不完全。这些结果表明，人癌细胞与原代培养的成纤维细胞之间通过两者分泌的可扩散因子存在相互生长依赖关系，且这些增强作用部分与癌细胞在体内的生长和转移有关。在体外临床可达到的浓度下，发现苏拉明对它们的相互作用具有抑制作用。
