방사선의학 웹진

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Abstract
The effect of cell cycle synchronisation on glucose metabolism in cancer cells is not known. We assessed how cell cycle synchronisation by thiazolidinediones (TZDs) can affect glucose uptake by cancer cells and investigated the anti-cancer effect of combination therapy with TZDs and 2-deoxy-glucose (2-DG) in colon cancer cells and in mouse xenograft models. Troglitazone (58.1 ± 2.0 vs 48.6 ± 1.3%, p = 0.002) or pioglitazone (82.9 ± 1.9 vs 61.6 ± 3.4%, p < 0.001) induced cell cycle arrest in SW480 cells at G1 phase. Western blot analysis showed the degradation of cyclin D1 and CDK4, and an increase in the expression levels of p21 and p27 after TZDs treatment. Withdrawal of troglitazone treatment induced significant increase in cellular 3H-DG uptake (141.5% ± 12.9% of controls) and membrane GLUT1 expression levels (146.3% of controls) by 24 h; 1 mM 2-DG treatment alone decreased cell survival by 5.8% as compared with the controls.; however, combination therapy enhanced the anti-tumour effects to 34.6% or 20.3% as compared with control cells. In vivo, each combination treatment group showed significant anti-tumour effects unlike the 2-DG alone group. Cell cycle synchronisation using TZDs induced cellular glucose uptake, which significantly enhanced the therapeutic effect of 2-DG in colon cancer.

Author information

Yoon JK1, Byeon HE2, Ko SA1, Park BN1, An YS1, Lee HY3, Lee YW3, Lee SJ4.
1
Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Republic of Korea.
2
Institute of Medical Science, Ajou University School of Medicine, Suwon, Republic of Korea.
3
Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
4
Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, Republic of Korea. suesj202@ajou.ac.kr.