Mareel M M, De Brabander M J
J Natl Cancer Inst. 1978 Sep;61(3):787-92.
The malignant C3H/3T3 mouse cells MO4 invaded embryonic chick heart fragments in an organotypic coculture system on semisolid medium, which mimicked malignant invasion. In this system, at a dose of 1 microgram/ml, the microtubule inhibitors colchicine, demecolcine, vincristine sulfate, vinblastine sulfate, or methyl[5-(2-thienylcarbonyl)-1H-benzimidazol-1-yl]-carbamate (Nocodazole) totally inhibited malignant invasion. At the same dose the drugs were also mitostatic, which was apparent from C-mitoses and from the absence of postmetaphase figures. At a mitostatic dose of 10 microgram/ml, 5-fluorouracil (FUra), cytosine arabinoside, or bleomycin did not interfere with malignant invasion. Combined treatment of the cocultures with the antimetabolite FUra (10 microgram/ml) plus the microtubule inhibitor Nocodazole (1 microgram/ml) completely inhibited invasion. These cocultures also showed the effective inhibition of mitosis by FUra, because Nocodazole-induced C-mitoses were absent. The reversibility of the anti-invasive effect of 4-day treatment with Nocodazole (1 microgram/ml) was demonstrated in shaker cocultures with the use of fluid medium. Our in vitro experiments indicated that cytoplasmic microtubules were involved in malignant invasion and that cell division and invasion constituted separate characteristics of malignant cells.
恶性C3H/3T3小鼠细胞MO4在半固体培养基上的器官型共培养系统中侵袭了胚胎鸡心脏组织块，该系统模拟了恶性侵袭过程。在这个系统中，当秋水仙碱、去乙酰秋水仙碱、硫酸长春新碱、硫酸长春碱或甲基[5-(2-噻吩基羰基)-1H-苯并咪唑-1-基] -氨基甲酸酯（诺考达唑）等微管抑制剂的剂量为1微克/毫升时，能完全抑制恶性侵袭。在相同剂量下，这些药物也具有有丝分裂抑制作用，这从C-有丝分裂以及后期后图像的缺失可以明显看出。当5-氟尿嘧啶（FUra）、阿糖胞苷或博来霉素的有丝分裂抑制剂量为10微克/毫升时，它们并不干扰恶性侵袭。用抗代谢物FUra（10微克/毫升）加微管抑制剂诺考达唑（1微克/毫升）联合处理共培养物，可完全抑制侵袭。这些共培养物也显示出FUra对有丝分裂的有效抑制作用，因为不存在诺考达唑诱导的C-有丝分裂。在使用液体培养基的摇床共培养中，证明了用诺考达唑（1微克/毫升）进行4天处理的抗侵袭作用是可逆的。我们的体外实验表明，细胞质微管参与了恶性侵袭，并且细胞分裂和侵袭构成了恶性细胞的不同特征。
