Teo Ka Yaw, Han Bumsoo
Department of Mechanical and Aerospace Engineering, University of Texas at Arlington, Arlington, TX 76019, USA.
J Biomech Eng. 2009 Jul;131(7):074513. doi: 10.1115/1.3153325.
The efficacy of chemotherapy is significantly impaired by the multidrug resistance (MDR) of cancer cells. The mechanism of MDR is associated with the overexpression of certain adenosine triphosphate-binding cassette protein transporters in plasma membranes, which actively pump out cytotoxic drugs from the intracellular space. In this study, we tested a hypothesis that freezing and thawing (F/T) may enhance intracellular drug delivery to MDR cancer cells via F/T-induced denaturation of MDR-associated proteins and/or membrane permeabilization. After a human MDR cancer cell line (NCI/ADR-RES) was exposed to several F/T conditions, its cellular drug uptake was quantified by a fluorescent calcein assay using calcein as a model drug. After F/T to -20 degrees C, the intracellular uptake of calcein increased by 70.1% (n=5, P=0.0004). It further increased to 118% as NCI/ADR-RES cells were frozen/thawed to -40 degrees C (n=3, P=0.009). These results support the hypothesis, and possible mechanisms of F/T-enhanced intracellular drug delivery were proposed and discussed.
癌细胞的多药耐药性（MDR）显著削弱了化疗的疗效。MDR的机制与质膜中某些三磷酸腺苷结合盒蛋白转运体的过表达有关，这些转运体可将细胞毒性药物从细胞内空间主动泵出。在本研究中，我们测试了一个假设，即冻融（F/T）可能通过F/T诱导的MDR相关蛋白变性和/或膜通透性增加，增强细胞内药物向MDR癌细胞的递送。将人MDR癌细胞系（NCI/ADR-RES）暴露于几种F/T条件后，以荧光素为模型药物，通过荧光素酶检测法定量其细胞药物摄取。在冻融至-20℃后，荧光素的细胞内摄取增加了70.1%（n=5，P=0.0004）。当NCI/ADR-RES细胞冻融至-40℃时，其摄取进一步增加至118%（n=3，P=0.009）。这些结果支持了该假设，并提出并讨论了F/T增强细胞内药物递送的可能机制。
