Ciomei M, Pastori W, Capolongo L, Geroni C, Melegaro G, Pennella G, Grandi M
Pharmacia, R&D/B.A. Pharmaceuticals, Experimental Oncology Department, Nerviano MI-Italy.
Br J Cancer. 1995 Dec;72(6):1504-8. doi: 10.1038/bjc.1995.537.
Resistance to FCE 24517 is not related to the emergence of any of the most frequently observed phenotypes. We have found that two resistant cell lines (L1210/24517 murine leukaemia and LoVo/24517 human colon adenocarcinoma) present congenital modifications in tyrosyl phosphatase and kinase activities. Moreover, the cytotoxic activity of FCE 24517 is increased in combination with a tyrosine phosphatase inhibitor and decreased in combination with protein kinase inhibitors, this being in agreement with the hypothesis that the activity of this drug is strictly dependent on the presence of tyrosine phosphorylated protein(s).
对FCE 24517的耐药性与任何最常观察到的表型的出现均无关。我们发现，两种耐药细胞系（L1210/24517小鼠白血病细胞系和LoVo/24517人结肠腺癌细胞系）在酪氨酸磷酸酶和激酶活性方面存在先天性改变。此外，FCE 24517与酪氨酸磷酸酶抑制剂联合使用时细胞毒性活性增强，与蛋白激酶抑制剂联合使用时细胞毒性活性降低，这与该药物的活性严格依赖于酪氨酸磷酸化蛋白的存在这一假设相符。
