文章基本信息

标题：Cell cycle synchronisation using thiazolidinediones affects cellular glucose metabolism and enhances the therapeutic effect of 2-deoxyglucose in colon cancer
本地全文：下载
作者：Joon-Kee Yoon ; Hye Eun Byeon ; Seung Ah Ko 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2020
卷号：10
期号：1
页码：1-7
DOI：10.1038/s41598-020-61661-4
出版社：Springer Nature
摘要：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.