Role of the calmodulin inhibitor trifluoperazine on the induction and expression of cell cycle traverse perturbations and cytotoxicity of daunorubicin and doxorubicin (adriamycin) in doxorubicin-resistant P388 mouse leukaemia cells.
Role of the calmodulin inhibitor trifluoperazine on the induction and expression of cell cycle traverse perturbations and cytotoxicity of daunorubicin and doxorubicin (adriamycin) in doxorubicin-resistant P388 mouse leukaemia cells.
复制标题
钙调蛋白抑制剂三氟嗪在细胞周期遍及扰动的诱导和表达中的作用，以及在耐二莫比霉素抗毒素的p388 P388小鼠白血病细胞中daunorubicin和doxorubicin（adriamycin）的细胞毒性。
DOI：
10.1038/bjc.1986.88
复制
发表时间：
1986-04
影响因子：
8.8
通讯作者：
Valenzuela R
中科院分区：
文献类型：
--
作者：
Ganapathi R;Yen A;Grabowski D;Schmidt H;Turinic R;Valenzuela R
阿霉素和柔红霉素是临床上重要的两种蒽环类抗肿瘤药物（Muggia & rosenweig, 1983）。多柔比星（DOX）和柔比星（DAU）获得性耐药的发展是与化疗重复疗程相关的一个严重问题，许多研究集中于确定DOX耐药和DAU耐药细胞的特征并评估规避耐药的方法（Dano, 1976; Ganapathi & Grabowski, 1983; Inaba & Johnson, 1978; Riehm & Biedler, 1972; Skovsgaard, 1980； Tsuruo等，1982）。在DOX耐药和DAU耐药的肿瘤模型中，对DAU和DOX的细胞毒性作用的抵抗被认为是由于细胞积累和/或药物保留减少（Inaba等人，1979;Skovsgaard, 1978）。细胞药物水平降低的现象是一种耐药机制，研究证实，用Tween 80、钙调素抑制剂和钙拮抗剂增加DAU和DOX的细胞积累可以显著增强细胞毒性反应（Ganapathi & Grabowski, 1983; Inaba & Johnson, 198; Riehm & Biedler, 1972； Tsuruo等，1982）。然而，细胞内蒽环类药物水平与耐药性之间的关系并不适用于强性亲脂蒽环类药物，它们在dox敏感细胞和dox耐药细胞中积累的程度相似（Ganapathi et al., 1984a）。此外，由于钙调素抑制剂三氟拉嗪（TFP）的存在增强了细胞毒性，因此仅在强而非弱DNA结合抗肿瘤药物中观察到（Ganapathi等，1984a; 1985a）
Doxorubicin (Adriamycin) and daunorubicin are two clinically importantanthracycline antitumour drugs (Muggia & Rosencweig, 1983). The development of acquired resistance to doxorubicin (DOX) and daunorubicin (DAU) is a serious problem associated with repeated courses of chemotherapy, and numerous studies have focussed on determining the characteristics of DOX-resistant and DAU-resistant cells and evaluating approaches to circumvent resistance (Dano, 1976; Ganapathi & Grabowski, 1983; Inaba & Johnson, 1978; Riehm & Biedler, 1972; Skovsgaard, 1980; Tsuruo et al., 1982). In DOX-resistant and DAU-resistant tumour models, resistanceto the cytotoxic effects of DAU and DOX has been suggested to be due to reduced cellular accumulation and/or retention of drug (Inaba et al., 1979; Skovsgaard, 1978). The phenomenon of reduced cellular drug levels as a mechanism of resistance is substantiated by studies which have demonstrated that augmentation of cellular accumulation of DAU and DOX with Tween 80, calmodulin inhibitors and calcium antagonists can significantly enhance the cytotoxic response (Ganapathi & Grabowski, 1983; Inaba & Johnson, 198; Riehm & Biedler, 1972; Tsuruo et al., 1982). The relationship, however, between cellular anthracycline levels and resistance is not true for the potent lipophilic anthracyclines, which are accumulated to a similar extent by DOX-sensitive and DOX-resistant cells (Ganapathi et al., 1984a). Furthermore, since enhanced cytotoxicity in the presence of the calmodulin inhibitor trifluoperazine (TFP) is observed only with strong and not weak DNA binding antitumoragents (Ganapathi et al., 1984a; 1985a), the mechanism (s) of resistance to