DIFFERENTIAL INVITRO SENSITIVITY OF HUMAN TUMOR AND NORMAL-CELLS TO CHEMOTHERAPEUTIC-AGENTS AND RESISTANCE MODULATORS
DIFFERENTIAL INVITRO SENSITIVITY OF HUMAN TUMOR AND NORMAL-CELLS TO CHEMOTHERAPEUTIC-AGENTS AND RESISTANCE MODULATORS
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DOI：
10.1002/ijc.2910480419
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发表时间：
1991-06-19
影响因子：
6.4
通讯作者：
LARSSON, R
中科院分区：
文献类型：
--
作者：
NYGREN, P;LARSSON, R
比较了对长春新碱（Vcr）本质耐药的人肾腺癌细胞系ACHN、人急性淋巴细胞白血病细胞系L0、其超过100倍的Vcr耐药亚系L100、正常人成纤维细胞和淋巴细胞，以及来自慢性淋巴细胞白血病（CLL）、急性髓细胞白血病（AML）和实体瘤患者的肿瘤细胞对细胞毒性的敏感性药物和耐药调节剂（RM）。 L100 细胞对单独的 RM 维拉帕米 (Ver)、环孢菌素 A (CsA) 和丁硫氨酸亚砜亚胺 (BSO) 以及顺铂表现出明显的敏感性，而 L0 和 ACHN 细胞（也是缓慢生长的成纤维细胞和非增殖淋巴细胞）的敏感性相当低。 与AML细胞和淋巴细胞相比，CLL细胞对单独的Ver和CsA更敏感。 Ver 和 CsA 在 Vcr 抗性 ACHN 和 L100 中显着增加了 Vcr 的细胞毒性，而且在敏感的 L0 细胞中也显着增加了 Vcr 的细胞毒性，而对 Dox 和 Vp-16 毒性的影响较小。 成纤维细胞和淋巴细胞通常对细胞毒性剂有抵抗力，添加 RM 仅产生很小的影响。 与正常淋巴细胞相比，CLL 细胞对 Dox 和 Vcr 更敏感，并且 Ver 和 CsA 增强了 Vcr 效应。 Ver 和 CsA 增强了来自恶性神经鞘瘤的非增殖 Vcr 抗性细胞中的 Vcr 效应，而这对来自肾腺癌的细胞没有影响。 我们得出的结论是，单独的 RM 的细胞毒性不依赖于肿瘤细胞的增殖率，并且 RM 的细胞毒性药物的增强作用可能对肿瘤细胞具有选择性，无论其初始水平和耐药模式如何。
The intrinsically Vincristine(Vcr)-resistant human kidney adenocarcinoma cell line ACHN, the human acute lymphoblastic leukemia cell line L0, its more-than-100-fold Vcr-resistant subline L100, normal human fibroblasts and lymphocytes, also tumor cells from patients with chronic lymphocytic leukemia (CLL), acute myeloblastic leukemia (AML) and solid tumors, were compared for sensitivity to cytotoxic drugs and resistance modulators (RMs). The L100 cells showed pronounced sensitivity to the RMs verapamil (Ver), cyclosporin A (CsA) and buthionine sulfoximine (BSO) alone as well as to cisplatinum, whereas the L0 and ACHN cells, also slowly growing fibroblasts and non-proliferating lymphocytes, were considerably less sensitive. Compared with AML cells and lymphocytes, CLL cells were more sensitive to Ver and CsA alone. The cytotoxicity of Vcr was significantly increased in the Vcr-resistant ACHN and L100, but also in sensitive L0 cells by Ver and CsA, with smaller effects on Dox and Vp-16 toxicity. Fibroblasts and lymphocytes were generally resistant to the cytotoxic agents and RM addition had only minor effects. CLL cells were more sensitive to Dox and Vcr as compared with normal lymphocytes, with potentiation of the Vcr effect by Ver and CsA. The Vcr effect in non-proliferating Vcr-resistant cells from a malignant schwannoma was potentiated by Ver and CsA, which had no effect in cells from a kidney adenocarcinoma. We conclude that cytotoxicity of RMs alone is not dependent on the proliferation rate of tumor cells and that potentiation of cytotoxic drugs by RMs may be selective for tumor cells irrespective of their initial level and mode of drug resistance.