The direct mapping of the uptake of platinum anticancer agents in individual human ovarian adenocarcinoma cells using a hard X-ray microprobe.
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.
Ilinski
Petr
P
Experimental Facilities Division, Argonne National Laboratory, Argonne, Illinois 60439, USA.
Lai
Barry
B
Cai
Zhonghou
Z
Yun
Wenbing
W
Legnini
Daniel
D
Talarico
Teresa
T
Cholewa
Marian
M
Webster
Lorraine K
LK
Deacon
Glen B
GB
Rainone
Silvina
S
Phillips
Don R
DR
Stampfl
Anton P J
AP
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D002945:Cisplatin / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004577:Electron Probe Microanalysis / Q000379:methods*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002945:Cisplatin