수종의 암세포에서 Verapamil이 Tc-99m MIBI와 Tetrofosmin의 섭취에 미치는 영향 (Effect of Verapamil on Cellular Uptake of Tc-99m MIBI and Tetrofosmin on Several Cancer Cells) |
Author |
김대현, 유정아, 서명랑, 배진호, 정신영, 안병철, 이규보, 이재태, |
Dae-Hyun Kim, MD, Jung-Ah Yoo, PhD, Jin-Ho Bae, MD, Shin Young Jeong, MD,Myung-Rang Suh, Byeong-Cheol Ahn, MD, Kyu Bo Lee, MD, Jaetae Lee, MD |
Affiliation |
경북대학교 의과대학 핵의학교실 Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, Korea |
Abstract |
Purpose: Cellular uptake of 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin (TF) is low in cancer cells
expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil
is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different
effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil
on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Cellular uptakes of
Tc-99m MIBI and TF were measured in erythroleukemia K562 cell, breast cancer MCF7 cell, and human
ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells.
RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and
to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were
evaluated at different concentrations upto 200 μM at 1×106 cells/㎖at 37℃. Radioactivity in supernatant and
pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was
measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer
cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr)
cell at a concentration of 100 μM and the maximal increase at 50 μM was 10-times to baseline. In contrast,
uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a
concentration over 1 μM. With a concentration of 200 μM verapamil, MIBI and TF uptakes in K562 cells
were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and
TF in MCF7 and SK-OV-3 cells were not changed with 10 μM, but were also decreased with verapamil
higher than 10 μM, resulting 40% and 5% of baseline at 50 μM. MTT assay of four cells revealed that K562,
MCF7, SK-OV3 were not damaged with verapamil at 200 μM. Conclusion: Although verapamil increases
uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in
certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes
of both tracers might differ among different cells, and interpretation of changes in tracer uptake with
verapamil in vitro should be different when different cell lines are used. |
Keyword |
verapamil, Tc-99m MIBI, tetrofosmin, multidrug resistance, cancer |
Full text Article |
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