抑制剂磷酸果糖激酶.PPT

WARBURG EFFECT Cancer cells tend to convert most glucose to lactate via Glycolysis regardless of whether oxygen is present. Definition of Warburg Effect Metabolic characteristics of tumor cells under Warburg Effect Anticancer treatment based on Warburg Effect We are going to talk about… When cancer occurs: 血管供应营养与氧气不足 坏死区（Necrosis） 低氧区（Hypoxia） 有氧区（Palisade） 糖酵解作用大幅增强 Definition of Warburg Effect *This property is shared by normal proliferating(增殖) tissues. Definition of Warburg Effect “Warburg effect is the observation that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, rather than by a comparatively low rate of glycolysis followed by oxidation of pyruvate in mitochondria like most normal cells. The latter process is aerobic (uses oxygen). Malignant（恶性的） rapidly-growing tumor cells typically have glycolytic rates that are up to 200 times higher than those of their normal tissues of origin; this occurs even if oxygen is plentiful. ” Definition of Warburg Effect 1.线粒体呼吸功能下降 Metabolic characteristics of tumor cells under WE 2.磷酸果糖激酶-2（PFK-2）表达增高 Metabolic characteristics of tumor cells under WE 3.己糖激酶（HK）的活性增强。 I 型 脑组织， II型 胰岛素敏感型，脂肪及肌组织。 III型 肝、肾和肠组织中微量表达。 IV型 （Glucokinase）仅在肝和胰中。 Metabolic characteristics of tumor cells under WE Hexokinase II Metabolic characteristics of tumor cells under WE 另外，HK的表达增强也和AKt原癌基因表达增强有关。 己糖激酶(Hexokinase)抑制剂 磷酸果糖激酶-1(PFK-1)抑制剂 磷酸甘油醛脱氢酶(Glyceraldehyde phosphate dehydrogenase)抑制剂 乳酸脱氢酶(Lactate dehydrogenase)抑制剂 Anticancer treatment based on WE 1.己糖激酶(Hexokinase)抑制剂 2-脱氧葡萄糖（2-DG）：葡萄糖竞争性抑制剂。可以被己糖激酶磷酸化，成为磷酸2-脱氧葡萄糖（2-GD-p）在细胞中累积。抑制糖酵解第一步。在体外实验中，2-DG引起了肿瘤细胞ATP衰竭而死亡。但在临床治疗中效果有限。 葡萄糖类似物5-thio glucose： 与2-DG类似 ? 3-溴丙酮酸（3-BRPa）：体外实验与2-DG类似。临床上，静脉注射可以有效抑制肿瘤细胞扩散。此外在肺癌细胞中，有报道它还可以激活线粒体内细胞凋亡信号而导致肿瘤细胞凋亡。主要用于治疗肝癌。 Anticancer treatment based on WE 己糖激酶抑制剂还有： Na2SeO3 氯尼达明（Lonidamine） 伊马替尼 （Imatinib） Anticancer treatment based on WE 2.