Effect of calcium antagonists on the chemosensitivity of two multidrug-resistant human tumour cell lines which do not overexpress P-glycoprotein.
Effect of calcium antagonists on the chemosensitivity of two multidrug-resistant human tumour cell lines which do not overexpress P-glycoprotein.
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钙拮抗剂对两种不过度表达 P-糖蛋白的多重耐药人肿瘤细胞系化疗敏感性的影响。
作者：
Spc Cole;HF Downes;ML Slovak
我们研究了8种化合物增强两种人肿瘤细胞系（小细胞肺癌细胞系NCI-H69和纤维肉瘤细胞系HT 1080）及其多药耐药变体对阿霉素（ADM）敏感性的能力。耐药细胞系（H69 AR和HT 1080/DR 4）不过表达P-糖蛋白。维拉帕米，尼卡地平，马来酸哌己西林，氯喹，他莫昔芬，克罗米酚，异戊烯胺和三氟拉嗪单独和与ADM组合测试其细胞毒性作用。当单独测试这些药剂时，注意到亲本和抗性细胞系之间的敏感性没有重大差异，除了HT 1080/DR 4细胞对尼卡地平表现出轻微的附带敏感性和H69 AR细胞对氯喹和克罗米酚表现出交叉抗性。当化疗增敏剂与ADM组合时，没有观察到任何亲本细胞系的增强的细胞毒性。在HT 1080/DR 4细胞中，维拉帕米仅显示出适度的剂量依赖性化学增敏作用，而其他化合物则没有作用。维拉帕米和尼卡地平可轻度增强ADM对H69 AR细胞的杀伤作用，但这种作用不具有剂量依赖性。这些结果表明，维拉帕米和其他钙拮抗剂以剂量依赖性方式逆转耐药性并不是多药耐药肿瘤细胞的不变特性。
We have examined the ability of eight compounds to enhance adriamycin (ADM) sensitivity of two human tumour cell lines (a small cell lung cancer cell line, NCI-H69, and a fibrosarcoma cell line, HT1080) and their multidrug-resistant variants. The resistant cell lines (H69AR and HT1080/DR4) do not overexpress P-glycoprotein. Verapamil, nicardipine, perhexiline maleate, chloroquine, tamoxifen, clomiphene, prenylamine and trifluoperazine were tested alone and in combination with ADM for their cytotoxic effects. No major differences in sensitivity between the parent and resistant cell lines were noted when these agents were tested alone, except for HT1080/DR4 cells which exhibited a slight collateral sensitivity to nicardipine and H69AR cells which showed cross-resistance to chloroquine and clomiphene. When the chemosensitisers were combined with ADM no enhanced cytotoxicity of either parent cell line was observed. In HT1080/DR4 cells, verapamil showed only a modest dose-dependent chemosensitising effect while the other compounds had no effect. Verapamil and nicardipine enhanced ADM cytotoxicity in H69AR cells slightly but these effects were not dose-dependent. These results demonstrate that the reversal of drug resistance by verapamil and other calcium antagonists in a dose-dependent fashion is not an invariable property of multidrug-resistant tumour cells.
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影响因子：
8.8
作者：
Ganapathi R;Yen A;Grabowski D;Schmidt H;Turinic R;Valenzuela R
通讯作者：
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氯喹增强抗癌药物对多重耐药人白血病细胞的细胞毒性。
影响因子：
5.8
作者：
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通讯作者：
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影响因子：
11.2
作者：
William T. Beck;M. Cirtain;M. Danks;Ronald L. Felsted;Ahmad R. Safa;J. S. Wolverton;D. Suttle;Jeffrey M. Trent
通讯作者：
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膜转运系统之间的相互作用：蒽环类药物、钙拮抗剂和抗雌激素药物。
影响因子：
5.8
作者：
Kessel,D
通讯作者：
Kessel,D
维拉帕米和其他药物对蒽环类药物分布和耐药性逆转的影响。
影响因子：
11.2
作者：
Hindenburg,AA;Baker,MA;Gleyzer,E;Stewart,VJ;Case,N;Taub,RN
通讯作者：
Taub,RN