己糖激酶Ⅱ与肿瘤增殖及靶向治疗

Hexokinase-Ⅱ role in tumor growth and targeting therapy

肿瘤细胞所需能量主要来自有氧糖酵解途径，即Warburg效应，该生化过程同时为肿瘤细胞提供生长所需的大量前体物质。已糖激酶Ⅱ（HK—Ⅱ）为糖酵解的限速酶，在肿瘤组织中高表达，与肿瘤的能量代谢密切相关。近年来研究表明肿瘤细胞中的HK—Ⅱ不仅介导Warburg效应，还能抑制肿瘤细胞凋亡、调节自噬而发挥促进肿瘤增殖的作用。已在多种肿瘤细胞中证实，阻断HK-Ⅱ基因表达及应用HK-Ⅱ的小分子抑制剂均可起到杀伤肿瘤的作用，以HK—Ⅱ为靶点的抑制剂有可能成为新一代靶向药物。

The energy for tumor ceils mainly derives from the aerobic glycolysis, that is, the Warburg effect, which also provides a large amount of precursor substances for the growth of tumor cells. Hexokinase-Ⅱ （ HK- Ⅱ）, highly expressed in tumor tissue, is the rate-limiting enzyme of glycolysis and closely related to the energy metabolism of tumor. Recent studies have showed that HK-Ⅱ not only mediates Warburg effect, but also promotes tumor proliferation by inhibiting tumor cell apoptosis and regulating autophagy. It has been confirmed that blocking HK- Ⅱ gene expression and inhibiting HK-Ⅱ with small molecule inhibitor can kill tumor cells in many kinds of cancer. Agent targeting HK- Ⅱ may become a new generation of targeted drugs.