Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan.
Cancer Sci. 2010 Oct;101(10):2171-8. doi: 10.1111/j.1349-7006.2010.01670.x. Epub 2010 Jul 30.
Cisplatin is an effective chemotherapeutic agent for ovarian cancer, but the sensitivity of cancers differs in individual cases. Because cisplatin is reported to suppress glucose uptake, we investigated the correlation between glucose uptake and sensitivity to the drug. A fluorescent derivative of D-glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl) amino]-2-deoxyglucose), was used to evaluate glucose uptake. Two ovarian cancer cell lines, SKOV-3 as a relatively resistant line and OVCAR-3 as a relatively sensitive line, were analyzed. Both cell lines had a decreased number of cells accompanied by cell death 24 h after cisplatin treatment, but not at 3 h. In contrast, glucose uptake was decreased 3 h after high-dose cisplatin treatment, which correlated with the sensitivity to the drug at 24 h. The protein levels of glucose transporter 1 (GLUT1) did not change with cisplatin treatment. In contrast, the membrane localization of GLUT1 disappeared after cisplatin treatment. Other cisplatin-resistant cell lines did not show an early decrease in glucose uptake after cisplatin treatment. The early decrease in glucose uptake and later cell death also correlated in cultured cancer cells from ovarian cancer patients. Thus, the decrease in glucose uptake at an early time point after high dose cisplatin treatment reflected cisplatin chemosensitivity in ovarian cancer cells. Measuring glucose uptake might be useful as a rapid evaluation of cisplatin chemosensitivity in ovarian cancer patients.
顺铂是治疗卵巢癌的有效化疗药物,但癌症的敏感性在个体病例中有所不同。由于顺铂据报道能抑制葡萄糖摄取,我们研究了葡萄糖摄取与对药物敏感性之间的相关性。D-葡萄糖的荧光衍生物 2-NBDG(2-[N-(7-硝基苯并-2-氧代-1,3-二恶烷-4-基)氨基]-2-脱氧葡萄糖)用于评估葡萄糖摄取。分析了两种卵巢癌细胞系,即对顺铂相对耐药的 SKOV-3 系和相对敏感的 OVCAR-3 系。两种细胞系在顺铂处理 24 小时后,细胞数量减少伴随细胞死亡,但在 3 小时时没有。相比之下,高剂量顺铂处理 3 小时后葡萄糖摄取减少,与 24 小时时对药物的敏感性相关。葡萄糖转运蛋白 1(GLUT1)的蛋白水平在顺铂处理后没有变化。相比之下,GLUT1 的膜定位在顺铂处理后消失。其他顺铂耐药细胞系在顺铂处理后没有表现出葡萄糖摄取的早期减少。在卵巢癌患者培养的癌细胞中,葡萄糖摄取的早期减少与随后的细胞死亡也相关。因此,高剂量顺铂处理后早期葡萄糖摄取的减少反映了卵巢癌细胞对顺铂的化疗敏感性。测量葡萄糖摄取可能有助于快速评估卵巢癌患者对顺铂的化疗敏感性。