Lee S C, Deutsch C, Beck W T
Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.
Proc Natl Acad Sci U S A. 1988 Mar;85(6):2019-23. doi: 10.1073/pnas.85.6.2019.
Tumor cell lines selected to grow in the presence of one "natural product" antineoplastic drug often develop cross-resistance to others. This multidrug resistance (MDR) is believed to be a major problem in cancer therapy. Organic Ca2+-channel blockers, such as verapamil, can reverse this resistance and render MDR cells in culture nearly as sensitive to the antineoplastic drugs as the drug-sensitive cells from which they were derived. It has therefore been suggested that Ca2+ channels may play a role in MDR. To determine directly whether there are electrophysiological correlates of MDR, we used whole-cell and single-channel patch-clamp techniques to survey the ion channels in a drug-sensitive human T-cell leukemia line, CCRF-CEM, and a MDR variant, CEM/VLB100. We found no evidence for a voltage-gated Ca2+ channel. However, we did identify three other current/channel types: a voltage-gated tetrodotoxin-sensitive inward current carried by Na+, a voltage-gated labile outward current carried by K+, and a nonselective cation channel reversing at 0 mV. Drug-sensitive and -resistant cells were the same with respect to the level of expression of these channels.
被选择在一种“天然产物”抗肿瘤药物存在的情况下生长的肿瘤细胞系，常常会对其他药物产生交叉耐药性。这种多药耐药性（MDR）被认为是癌症治疗中的一个主要问题。有机钙通道阻滞剂，如维拉帕米，能够逆转这种耐药性，并使培养中的多药耐药细胞对抗肿瘤药物的敏感性几乎与产生它们的药物敏感细胞一样。因此，有人提出钙通道可能在多药耐药中起作用。为了直接确定多药耐药是否存在电生理相关性，我们使用全细胞和单通道膜片钳技术来检测一种药物敏感的人T细胞白血病细胞系CCRF - CEM和一个多药耐药变体CEM/VLB100中的离子通道。我们没有发现电压门控钙通道存在的证据。然而，我们确实鉴定出了其他三种电流/通道类型：一种由Na⁺携带的电压门控河豚毒素敏感内向电流、一种由K⁺携带的电压门控不稳定外向电流，以及一种在0 mV处反转的非选择性阳离子通道。在这些通道的表达水平方面，药物敏感细胞和耐药细胞是相同的。
