Lollini P L, De Giovanni C, Del Re B, Landuzzi L, Nicoletti G, Prodi G, Scotlandi K, Nanni P
Istituto di Cancerologia, Bologna, Italy.
Cancer Res. 1989 Jul 1;49(13):3631-6.
The effect of various antineoplastic drugs (1-beta-D-arabinofuranosylcytosine, 5-azacytidine, cisplatin, dactinomycin, epirubicin, vincristine, and the activated metabolite of cyclophosphamide, mafosfamide) on cell differentiation in vitro was investigated using a human alveolar rhabdomyosarcoma cell clone, RMZ-RC2. These cells are able to differentiate spontaneously from small mononuclear proliferating elements to terminal, extremely elongated multinuclear structures resembling myotubes; morphological differentiation is accompanied by the expression of myosins, in particular the embryonic isoform, which was used in this study as a specific marker of myogenic differentiation. The proportion of differentiated myosin-positive cells, which was around 10-15% in control cultures 10-15 days after seeding, was increased by some drug treatments up to 30-40%; the proportion of multinuclear elements was also increased. 1-beta-D-arabinofuranosylcytosine and 5-azacytidine were the most effective drugs, while dactinomycin had no effect; other molecules ranked in between. Since significant increments were usually observed after treatment with drug doses inhibiting cell growth, the kinetic behavior of the absolute number of myosin-positive cells or nuclei was analyzed to assess whether some effects could be due to a negative selection of proliferating, undifferentiated cells. This appeared to be the case for vincristine and epirubicin, while 1-beta-D-arabinofuranosylcytosine, 5-azacytidine, and, to a lesser degree, mafosfamide and cisplatin actually seemed to increase differentiation ability.
使用人肺泡横纹肌肉瘤细胞克隆RMZ-RC2，研究了各种抗肿瘤药物（1-β-D-阿拉伯呋喃糖基胞嘧啶、5-氮杂胞苷、顺铂、放线菌素D、表柔比星、长春新碱以及环磷酰胺的活化代谢产物马磷酰胺）对体外细胞分化的影响。这些细胞能够自发地从小的单核增殖细胞分化为终末的、极度伸长的多核结构，类似于肌管；形态学分化伴随着肌球蛋白的表达，特别是胚胎异构体，在本研究中用作成肌分化的特异性标志物。接种后10 - 15天，对照培养物中分化的肌球蛋白阳性细胞比例约为10 - 15%，一些药物处理可将其提高至30 - 40%；多核细胞的比例也增加。1-β-D-阿拉伯呋喃糖基胞嘧啶和5-氮杂胞苷是最有效的药物，而放线菌素D没有效果；其他分子的效果介于两者之间。由于通常在用抑制细胞生长的药物剂量处理后观察到显著增加，因此分析了肌球蛋白阳性细胞或细胞核绝对数量的动力学行为，以评估某些效应是否可能是由于对增殖的未分化细胞的负选择所致。长春新碱和表柔比星似乎是这种情况，而1-β-D-阿拉伯呋喃糖基胞嘧啶、5-氮杂胞苷以及程度较轻的马磷酰胺和顺铂实际上似乎增加了分化能力。
