Martin S K, Oduola A M, Milhous W K
Science. 1987 Feb 20;235(4791):899-901. doi: 10.1126/science.3544220.
The parasite Plasmodium falciparum, like neoplastic cells, develops resistance to multiple structurally unrelated drugs. If the mechanisms by which P. falciparum and neoplastic cells become resistant are similar, then it may be possible to reverse the resistance in the two types of cells by the same pharmacological agents. Verapamil, a calcium channel blocker, completely reversed chloroquine resistance in two chloroquine-resistant P. falciparum clones from Southeast Asia and Brazil. Verapamil reversed chloroquine resistance at the same concentration (1 X 10(-6)M) as that at which it reversed resistance in multidrug-resistant cultured neoplastic cells. This same concentration of verapamil had no effect on chloroquine-sensitive parasites. Hence, chloroquine resistance in P. falciparum may fit the criteria for the multidrug-resistant phenotype.
恶性疟原虫这种寄生虫,与肿瘤细胞一样,会对多种结构不相关的药物产生耐药性。如果恶性疟原虫和肿瘤细胞产生耐药性的机制相似,那么或许有可能用相同的药理剂来逆转这两种细胞的耐药性。维拉帕米是一种钙通道阻滞剂,它能完全逆转来自东南亚和巴西的两个耐氯喹恶性疟原虫克隆株的氯喹耐药性。维拉帕米逆转氯喹耐药性的浓度(1×10⁻⁶M)与它逆转多药耐药培养肿瘤细胞耐药性的浓度相同。相同浓度的维拉帕米对氯喹敏感的寄生虫没有影响。因此,恶性疟原虫的氯喹耐药性可能符合多药耐药表型的标准。