腫瘤細胞能量代謝機理的研究進展_《中國普外基礎與臨床雜志》

作者：

郝朗松 ¹ , 張忠民 ¹ ,  伍曉汀 ²

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

關鍵詞：

Warburg效應缺氧誘導因子葡萄糖轉運體腫瘤內缺氧

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目的總結惡性腫瘤細胞能量代謝的研究進展。
方法復習相關資料，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定的能量來維持代謝。糖的攝取和糖酵解處于增高狀態是其生物學特征，葡萄糖轉運和代謝對腫瘤細胞至關重要，且導致不良的預后。
結論研究缺氧誘導相關基因與腫瘤的關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. 中國普外基礎與臨床雜志, 2010, 17(1): 97-101. doi: 復制

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. 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.

《中國普外基礎與臨床雜志》

腫瘤細胞能量代謝機理的研究進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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《中國普外基礎與臨床雜志》

腫瘤細胞能量代謝機理的研究進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料