Ilinski Petr, Lai Barry, Cai Zhonghou, Yun Wenbing, Legnini Daniel, Talarico Teresa, Cholewa Marian, Webster Lorraine K, Deacon Glen B, Rainone Silvina, Phillips Don R, Stampfl Anton P J
Experimental Facilities Division, Argonne National Laboratory, Argonne, Illinois 60439, USA.
Cancer Res. 2003 Apr 15;63(8):1776-9.
Uptake of platinum-based anticancer compounds into individual human ovarian andenocarcinoma cells was measured using an X-ray microprobe. The uptake of cisplatin, a platinum-based compound, in drug-resistant cells is decreased by approximately 50% after 24 h, compared with the uptake of the drug in nonresistant cells over the same time period. The Pt103 derivative of the drug, in contrast, showed an increased uptake by an order of magnitude in resistant cells over the same time period. Increased uptake appears to allow Pt103 to overcome the resistance mechanism developed by the cell. This work additionally shows that the X-ray microprobe is able to directly quantify Pt drug uptake on a subcellular level and can measure the mass of Pt down to a detectable limit of 20 attograms of Pt (2 x 10(-17) grams or 6 x 10(4) Pt atoms) in 1 s. Such exquisite elemental sensitivity combined with high spatial resolution paves the way for quantitative submicron three-dimensional mapping of elemental distributions within individual cells.
使用X射线微探针测量了铂基抗癌化合物进入人卵巢腺癌细胞个体的摄取情况。与相同时间段内非耐药细胞对顺铂(一种铂基化合物)的摄取相比,耐药细胞对顺铂的摄取在24小时后降低了约50%。相比之下,该药物的Pt103衍生物在相同时间段内耐药细胞中的摄取增加了一个数量级。摄取增加似乎使Pt103能够克服细胞产生的耐药机制。这项工作还表明,X射线微探针能够在亚细胞水平直接定量铂药物摄取,并且能够在1秒内测量低至20阿托克铂(2×10⁻¹⁷克或6×10⁴个铂原子)的可检测极限的铂质量。这种极高的元素灵敏度与高空间分辨率相结合,为单个细胞内元素分布的定量亚微米三维映射铺平了道路。