Ko Young H, Smith Barbara L, Wang Yuchuan, Pomper Martin G, Rini David A, Torbenson Michael S, Hullihen Joanne, Pedersen Peter L
The Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA.
Biochem Biophys Res Commun. 2004 Nov 5;324(1):269-75. doi: 10.1016/j.bbrc.2004.09.047.
A common feature of many advanced cancers is their enhanced capacity to metabolize glucose to lactic acid. In a challenging study designed to assess whether such cancers can be debilitated, we seeded hepatocellular carcinoma cells expressing the highly glycolytic phenotype into two different locations of young rats. Advanced cancers (2-3cm) developed and were treated with the alkylating agent 3-bromopyruvate, a lactate/pyruvate analog shown here to selectively deplete ATP and induce cell death. In all 19 treated animals advanced cancers were eradicated without apparent toxicity or recurrence. These findings attest to the feasibility of completely destroying advanced, highly glycolytic cancers.
许多晚期癌症的一个共同特征是其将葡萄糖代谢为乳酸的能力增强。在一项旨在评估此类癌症是否能够被抑制的具有挑战性的研究中，我们将表达高度糖酵解表型的肝癌细胞接种到幼鼠的两个不同部位。晚期癌症（2 - 3厘米）形成后，用烷基化剂3 - 溴丙酮酸进行治疗，在此显示该物质是一种乳酸/丙酮酸类似物，可选择性耗尽三磷酸腺苷（ATP）并诱导细胞死亡。在所有19只接受治疗的动物中，晚期癌症均被根除，且无明显毒性或复发。这些发现证明了完全摧毁晚期、高度糖酵解癌症的可行性。
