• 1.貴州省人民醫(yī)院普外科（貴陽 550002）;;
  • 2.四川大學(xué)華西醫(yī)院胃腸外科中心（成都 610041）;

目的  總結(jié)惡性腫瘤細胞能量代謝的研究進展。
方法  復(fù)習(xí)相關(guān)資料，就近年來惡性腫瘤細胞能量代謝的研究進展進行綜述。
結(jié)果  惡性腫瘤具有獨特的能量代謝特點，缺氧的腫瘤細胞生長和增殖需要穩(wěn)定的能量來維持代謝。糖的攝取和糖酵解處于增高狀態(tài)是其生物學(xué)特征，葡萄糖轉(zhuǎn)運和代謝對腫瘤細胞至關(guān)重要，且導(dǎo)致不良的預(yù)后。
結(jié)論  研究缺氧誘導(dǎo)相關(guān)基因與腫瘤的關(guān)系將有助于破解能量代謝的機理，為腫瘤的診斷和治療提供有力的證據(jù)及新的思路和途徑，改善既往的治療策略，給腫瘤患者更合理和個性化的治療。

引用本文： 郝朗松,張忠民,伍曉汀. 腫瘤細胞能量代謝機理的研究進展. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(1): 97-101. doi: 復(fù)制

1. Yeluri S, Madhok B, Prasad KR, et al. Cancer’s craving for sugar: an opportunity for clinical exploitation [J]. J Cancer Res Clin Oncol, 2009; 135(7): 867877.
2. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation [J]. Science, 2009; 324(5930): 10291033.
3. DeBerardinis RJ. Is cancer a disease of abnormal cellular metabolism? New angles on an old idea [J]. Genet Med, 2008; 10(11): 767777.
4. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? [J]. Nat Rev Cancer, 2004; 4(11): 891899.
5. Semenza GL. Hypoxia, clonal selection, and the role of HIF1 in tumor progression [J]. Crit Rev Biochem Mol Biol, 2000; 35(2): 71103.
6. Hoffmann JS, Cazaux C. DNA synthesis, mismatch repair and cancer [J]. Int J Oncol, 1998; 12(2): 377382.
7. Garber K. Energy deregulation: licensing tumors to grow [J]. Science, 2006; 312(5777): 11581159.
8. Kim JW, Gao P, Liu YC, et al. Hypoxiainducible factor 1 and dysregulated cMyc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1 [J]. Mol Cell Biol, 2007; 27(21): 73817393.
9. Stubbs M, Bashford CL, Griffiths JR. Understanding the tumor metabolic phenotype in the genomic era [J]. Curr Mol Med, 2003; 3(1): 4959.
10. Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond [J]. Cell, 2008; 134(5): 703707.
11. Bartrons R, Caro J. Hypoxia, glucose metabolism and the Warburg’s effect [J]. J Bioenerg Biomembr, 2007; 39(3): 223229.
12. Rastogi S, Banerjee S, Chellappan S, et al. Glut1 antibodies induce growth arrest and apoptosis in human cancer cell lines [J]. Cancer Lett, 2007; 257(2): 244251.
13. Horrée N, van Diest PJ, van der Groep P, et al. Hypoxia and angiogenesis in endometrioid endometrial carcinogenesis [J]. Cell Oncol, 2007; 29(3): 219227.
14. Mallick I, Sharma SC, Behera D, et al. Optimization of dose and fractionation of endobronchial brachytherapy with or without external radiation in the palliative management of nonsmall cell lung cancer: a prospective randomized study [J]. J Cancer Res Ther, 2006; 2(3): 119125.
15. Déry MA, Michaud MD, Richard DE. Hypoxiainducible factor 1: regulation by hypoxic and nonhypoxic activators [J]. Int J Biochem Cell Biol, 2005; 37(3): 535540.
16. Semenza GL. HIF1 mediates the Warburg effect in clear cell renal carcinoma [J]. J Bioenerg Biomembr, 2007; 39(3): 231234.
17. Lu H, Forbes RA, Verma A. Hypoxiainducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis [J]. J Biol Chem, 2002; 277(26): 2311123115.
18. Moeller BJ, Cao Y, Li CY, et al. Radiation activates HIF1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules [J]. Cancer Cell, 2004; 5(5): 429441.
19. Airley RE, Mobasheri A. Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics [J]. Chemotherapy, 2007; 53(4): 233256.
20. Macheda ML, Rogers S, Best JD. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer [J]. J Cell Physiol, 2005; 202(3): 654662.
21. Hoskin PJ, Sibtain A, Daley FM, et al. GLUT1 and CAⅨ as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON [J]. Br J Cancer, 2003; 89(7): 12901297.
22. Castro MA, Pozo M, Cortés C, et al. Intracellular ascorbic acid inhibits transport of glucose by neurons, but not by astrocytes [J]. J Neurochem, 2007; 102(3): 773782.
23. Copland JA, Pardini AW, Wood TG, et al. IGF1 controls GLUT3 expression in muscle via the transcriptional factor Sp1 [J]. Biochim Biophys Acta, 2007; 1769(1112): 631640.
24. Zhao FQ, Miller PJ, Wall EH, et al. Bovine glucose GLUT8: cloning, expression and developmental regulation in mammary gland [J]. Biochim Biophys Acta, 2004; 1680(2): 103113.
25. Chen C, Pore N, Behrooz A, et al. Regulation of glut1 mRNA by hypoxiainducible factor1. Interaction between Hras and hypoxia [J]. J Biol Chem, 2001; 276(12): 95199525.
26. Williams KJ, Telfer BA, Airley RE, et al. A protective role for HIF1 in response to redox manipulation and glucose deprivation: implications for tumorigenesis [J]. Oncogene, 2002; 21(2): 282290.
27. Bratasz A, Pandian RP, Deng Y, et al. In vivo imaging of changes in tumor oxygenation during growth and after treatment [J]. Magn Reson Med, 2007; 57(5): 950959.
28. Le QT, Kovacs MS, Dorie MJ, et al. Comparison of the comet assay and the oxygen microelectrode for measuring tumor oxygenation in headandneck cancer patients [J]. Int J Radiat Oncol Biol Phys, 2003; 56(2): 375383.
29. Bruehlmeier M, KaserHotz B, Achermann R, et al. Measurement of tumor hypoxia in spontaneous canine sarcomas [J]. Vet Radiol Ultrasound, 2005; 46(4): 348354.
30. Robey IF, Stephen RM, Brown KS, et al. Regulation of the Warburg effect in earlypassage breast cancer cells [J]. Neoplasia, 2008; 10(8): 745756.
31. Busk M, Horsman MR, Jakobsen S, et al. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage [J]. Eur J Nucl Med Mol Imaging, 2008; 35(12): 22942303.
32. Loncaster JA, Harris AL, Davidson SE, et al. Carbonic anhydrase (CAⅨ) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix [J]. Cancer Res, 2001; 61(17): 63946399.
33. Mamede M, El Fakhri G, AbreueLima P, et al. Preoperative estimation of esophageal tumor metabolic length in FDGPET images with surgical pathology confirmation [J]. Ann Nucl Med, 2007; 21(10): 553562.
34. Troost EG, Laverman P, Kaanders JH, et al. Imaging hypoxia after oxygenationmodification: comparing 18FFMISO autoradiography with pimonidazole immunohistochemistry in human xenograft tumors [J]. Radiother Oncol, 2006; 80(2): 157164.
35. Holdsworth CH, Badawi RD, Manola JB, et al. CT and PET: early prognostic indicators of response to imatinib mesylate in patients with gastrointestinal stromal tumor [J]. AJR Am J Roentgenol, 2007; 189(6): W324W330.
36. Mamede M, AbreuELima P, Oliva MR, et al. FDGPET/CT tumor segmentationderived indices of metabolic activity to assess response to neoadjuvant therapy and progressionfree survival in esophageal cancer: correlation with histopathology results [J]. Am J Clin Oncol, 2007; 30(4): 377388.
37. Chung JK, Lee YJ, Kim SK, et al. Comparison of [18F] fluorodeoxyglucose uptake with glucose transporter1 expression and proliferation rate in human glioma and nonsmallcell lung cancer [J]. Nucl Med Commun, 2004; 25(1): 1117.
38. Bos R, van Der Hoeven JJ, van Der Wall E, et al. Biologic correlates of (18) fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography [J]. J Clin Oncol, 2002; 20(2): 379387.
39. Kato H, Takita J, Miyazaki T, et al. Correlation of 18Ffluorodeoxyglucose(FDG) accumulation with glucose transporter (Glut1) expression in esophageal squamous cell carcinoma [J].Anticancer Res, 2003; 23(4): 32633272.
40. Nijsten MW, van Dam GM. Hypothesis: using the Warburg effect against cancer by reducing glucose and providing lactate [J]. Med Hypotheses, 2009; 73(1): 4851.
41. Scatena R, Bottoni P, Pontoglio A, et al. Glycolytic enzyme inhibitors in cancer treatment [J]. Expert Opin Investig Drugs, 2008; 17(10): 15331545.
42. Chen Z, Lu W, GarciaPrieto C, et al. The Warburg effect and its cancer therapeutic implications [J]. J Bioenerg Biomembr, 2007; 39(3): 267274.
  1. 1. Yeluri S, Madhok B, Prasad KR, et al. Cancer’s craving for sugar: an opportunity for clinical exploitation [J]. J Cancer Res Clin Oncol, 2009; 135(7): 867877.
  2. 2. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation [J]. Science, 2009; 324(5930): 10291033.
  3. 3. DeBerardinis RJ. Is cancer a disease of abnormal cellular metabolism? New angles on an old idea [J]. Genet Med, 2008; 10(11): 767777.
  4. 4. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? [J]. Nat Rev Cancer, 2004; 4(11): 891899.
  5. 5. Semenza GL. Hypoxia, clonal selection, and the role of HIF1 in tumor progression [J]. Crit Rev Biochem Mol Biol, 2000; 35(2): 71103.
  6. 6. Hoffmann JS, Cazaux C. DNA synthesis, mismatch repair and cancer [J]. Int J Oncol, 1998; 12(2): 377382.
  7. 7. Garber K. Energy deregulation: licensing tumors to grow [J]. Science, 2006; 312(5777): 11581159.
  8. 8. Kim JW, Gao P, Liu YC, et al. Hypoxiainducible factor 1 and dysregulated cMyc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1 [J]. Mol Cell Biol, 2007; 27(21): 73817393.
  9. 9. Stubbs M, Bashford CL, Griffiths JR. Understanding the tumor metabolic phenotype in the genomic era [J]. Curr Mol Med, 2003; 3(1): 4959.
  10. 10. Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond [J]. Cell, 2008; 134(5): 703707.
  11. 11. Bartrons R, Caro J. Hypoxia, glucose metabolism and the Warburg’s effect [J]. J Bioenerg Biomembr, 2007; 39(3): 223229.
  12. 12. Rastogi S, Banerjee S, Chellappan S, et al. Glut1 antibodies induce growth arrest and apoptosis in human cancer cell lines [J]. Cancer Lett, 2007; 257(2): 244251.
  13. 13. Horrée N, van Diest PJ, van der Groep P, et al. Hypoxia and angiogenesis in endometrioid endometrial carcinogenesis [J]. Cell Oncol, 2007; 29(3): 219227.
  14. 14. Mallick I, Sharma SC, Behera D, et al. Optimization of dose and fractionation of endobronchial brachytherapy with or without external radiation in the palliative management of nonsmall cell lung cancer: a prospective randomized study [J]. J Cancer Res Ther, 2006; 2(3): 119125.
  15. 15. Déry MA, Michaud MD, Richard DE. Hypoxiainducible factor 1: regulation by hypoxic and nonhypoxic activators [J]. Int J Biochem Cell Biol, 2005; 37(3): 535540.
  16. 16. Semenza GL. HIF1 mediates the Warburg effect in clear cell renal carcinoma [J]. J Bioenerg Biomembr, 2007; 39(3): 231234.
  17. 17. Lu H, Forbes RA, Verma A. Hypoxiainducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis [J]. J Biol Chem, 2002; 277(26): 2311123115.
  18. 18. Moeller BJ, Cao Y, Li CY, et al. Radiation activates HIF1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules [J]. Cancer Cell, 2004; 5(5): 429441.
  19. 19. Airley RE, Mobasheri A. Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics [J]. Chemotherapy, 2007; 53(4): 233256.
  20. 20. Macheda ML, Rogers S, Best JD. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer [J]. J Cell Physiol, 2005; 202(3): 654662.
  21. 21. Hoskin PJ, Sibtain A, Daley FM, et al. GLUT1 and CAⅨ as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON [J]. Br J Cancer, 2003; 89(7): 12901297.
  22. 22. Castro MA, Pozo M, Cortés C, et al. Intracellular ascorbic acid inhibits transport of glucose by neurons, but not by astrocytes [J]. J Neurochem, 2007; 102(3): 773782.
  23. 23. Copland JA, Pardini AW, Wood TG, et al. IGF1 controls GLUT3 expression in muscle via the transcriptional factor Sp1 [J]. Biochim Biophys Acta, 2007; 1769(1112): 631640.
  24. 24. Zhao FQ, Miller PJ, Wall EH, et al. Bovine glucose GLUT8: cloning, expression and developmental regulation in mammary gland [J]. Biochim Biophys Acta, 2004; 1680(2): 103113.
  25. 25. Chen C, Pore N, Behrooz A, et al. Regulation of glut1 mRNA by hypoxiainducible factor1. Interaction between Hras and hypoxia [J]. J Biol Chem, 2001; 276(12): 95199525.
  26. 26. Williams KJ, Telfer BA, Airley RE, et al. A protective role for HIF1 in response to redox manipulation and glucose deprivation: implications for tumorigenesis [J]. Oncogene, 2002; 21(2): 282290.
  27. 27. Bratasz A, Pandian RP, Deng Y, et al. In vivo imaging of changes in tumor oxygenation during growth and after treatment [J]. Magn Reson Med, 2007; 57(5): 950959.
  28. 28. Le QT, Kovacs MS, Dorie MJ, et al. Comparison of the comet assay and the oxygen microelectrode for measuring tumor oxygenation in headandneck cancer patients [J]. Int J Radiat Oncol Biol Phys, 2003; 56(2): 375383.
  29. 29. Bruehlmeier M, KaserHotz B, Achermann R, et al. Measurement of tumor hypoxia in spontaneous canine sarcomas [J]. Vet Radiol Ultrasound, 2005; 46(4): 348354.
  30. 30. Robey IF, Stephen RM, Brown KS, et al. Regulation of the Warburg effect in earlypassage breast cancer cells [J]. Neoplasia, 2008; 10(8): 745756.
  31. 31. Busk M, Horsman MR, Jakobsen S, et al. Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage [J]. Eur J Nucl Med Mol Imaging, 2008; 35(12): 22942303.
  32. 32. Loncaster JA, Harris AL, Davidson SE, et al. Carbonic anhydrase (CAⅨ) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix [J]. Cancer Res, 2001; 61(17): 63946399.
  33. 33. Mamede M, El Fakhri G, AbreueLima P, et al. Preoperative estimation of esophageal tumor metabolic length in FDGPET images with surgical pathology confirmation [J]. Ann Nucl Med, 2007; 21(10): 553562.
  34. 34. Troost EG, Laverman P, Kaanders JH, et al. Imaging hypoxia after oxygenationmodification: comparing 18FFMISO autoradiography with pimonidazole immunohistochemistry in human xenograft tumors [J]. Radiother Oncol, 2006; 80(2): 157164.
  35. 35. Holdsworth CH, Badawi RD, Manola JB, et al. CT and PET: early prognostic indicators of response to imatinib mesylate in patients with gastrointestinal stromal tumor [J]. AJR Am J Roentgenol, 2007; 189(6): W324W330.
  36. 36. Mamede M, AbreuELima P, Oliva MR, et al. FDGPET/CT tumor segmentationderived indices of metabolic activity to assess response to neoadjuvant therapy and progressionfree survival in esophageal cancer: correlation with histopathology results [J]. Am J Clin Oncol, 2007; 30(4): 377388.
  37. 37. Chung JK, Lee YJ, Kim SK, et al. Comparison of [18F] fluorodeoxyglucose uptake with glucose transporter1 expression and proliferation rate in human glioma and nonsmallcell lung cancer [J]. Nucl Med Commun, 2004; 25(1): 1117.
  38. 38. Bos R, van Der Hoeven JJ, van Der Wall E, et al. Biologic correlates of (18) fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography [J]. J Clin Oncol, 2002; 20(2): 379387.
  39. 39. Kato H, Takita J, Miyazaki T, et al. Correlation of 18Ffluorodeoxyglucose(FDG) accumulation with glucose transporter (Glut1) expression in esophageal squamous cell carcinoma [J].Anticancer Res, 2003; 23(4): 32633272.
  40. 40. Nijsten MW, van Dam GM. Hypothesis: using the Warburg effect against cancer by reducing glucose and providing lactate [J]. Med Hypotheses, 2009; 73(1): 4851.
  41. 41. Scatena R, Bottoni P, Pontoglio A, et al. Glycolytic enzyme inhibitors in cancer treatment [J]. Expert Opin Investig Drugs, 2008; 17(10): 15331545.
  42. 42. Chen Z, Lu W, GarciaPrieto C, et al. The Warburg effect and its cancer therapeutic implications [J]. J Bioenerg Biomembr, 2007; 39(3): 267274.