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WARBURG EFFECT

Cancer cells tend to convert most glucose to lactate via Glycolysis regardless of whether oxygen is present. WARBURG EFFECT. We are going to talk about…. Definition of Warburg Effect Metabolic characteristics of tumor cells under Warburg Effect

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WARBURG EFFECT

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  1. Cancer cells tend to convert most glucose to lactate via Glycolysis regardless of whether oxygen is present. WARBURG EFFECT

  2. We are going to talk about… • Definition of Warburg Effect • Metabolic characteristics of tumor cells under Warburg Effect • Anticancer treatment based on Warburg Effect

  3. Definition of Warburg Effect • 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

  4. Definition of Warburg Effect *This property is shared by normal proliferating(增殖) tissues.

  5. 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. ”

  6. Metabolic characteristics of tumor cells under WE 1.线粒体呼吸功能下降

  7. Metabolic characteristics of tumor cells under WE 2.磷酸果糖激酶-2（PFK-2）表达增高

  8. 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。 Hexokinase II

  9. Metabolic characteristics of tumor cells under WE

  10. 另外，HK的表达增强也和AKt原癌基因表达增强有关。另外，HK的表达增强也和AKt原癌基因表达增强有关。

  11. 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

  12. Anticancer treatment based on WE

  13. 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。

  14. 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）

  15. Anticancer treatment based on WE 2.磷酸果糖激酶-1(PFK-1)抑制剂： 左旋咪唑(Levamisole) 3.磷酸甘油醛脱氢酶(Glyceraldehyde phosphate Dehydrogenase)抑制剂: 丙酮醛(Methylglyoxal) 4.乳酸脱氢酶(Lactate dehydrogenase)抑制剂： 黄嘌呤核苷(Inosine)在治疗胃癌时效果明显。

  16. Anticancer treatment based on WE 以上几种抑制糖酵解途径而治疗癌症的药物只在体外实验中有明显的效果，将它们单独应用于癌症的治疗，达不到预期疗效。临床上多将以上几种药物配合，并结合其他的治疗手段一起使用。

  17. References [1]谢运. (2009). Akt及其在肿瘤细胞糖酵解中的作用. 国际肿瘤学杂志, 36 (10), 751-754. [2]沈万方. (2007). 低氧微环境中肿瘤的能量代谢. 生命的化学, 27 (1), 58-60. [3]赵迎超. (2006). 己糖激酶与恶性肿瘤关系的研究进展. 肿瘤防治研究, 33 (9), 694-696. [4]邹满意. (2006). 糖酵解酶抑制剂抗肿瘤作用的研究进展. 武警医学院学报, 15 (3), 286-288. [5]慕容. (2009). 肿瘤细胞的糖酵解机制与基于糖酵解的肿瘤治疗策略. 药物生物技术, 16 (6), 573-577. [6]Heiden, M. G. (2009). Understanding the Warburg Effect: The metabolic requirements of cell proliferation. Science, 324, 1029. [7]Mathupala, S. P. (2006). Hexokinase II: Cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene , 4777-4786. [8]Mitochondria: not just innocent bystanders. (n.d.). Retrieved from ScienceDirect: http://www.sciencedirect.com/ 

  18. 朱可昊陈乃修廖洪蔚马炎 WARBURG EFFECT THANK YOU

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