Intracellular acidification of human melanoma xenografts by the respiratory inhibitor m-iodobenzylguanidine plus hyperglycemia: a 31P magnetic resonance spectroscopy study.
Intracellular acidification of human melanoma xenografts by the respiratory inhibitor m-iodobenzylguanidine plus hyperglycemia: a 31P magnetic resonance spectroscopy study.
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发表时间：
2000-07
期刊：
影响因子：
11.2
通讯作者：
R. Zhou;N. Bansal;D. Leeper;J. Glickson
中科院分区：
文献类型：
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作者：
R. Zhou;N. Bansal;D. Leeper;J. Glickson
在体内31 P磁共振波谱表明，人类黑色素瘤异种移植物可以显着酸化诱导高血糖症与管理的间碘苄胍（MIBG），线粒体呼吸抑制剂相结合。在黑色素瘤异种移植物中（直径≤ 8 mm），细胞内pH（pHi，通过Pi共振的化学位移测量）和细胞外pH（pHe，用3-氨基丙基膦酸酯测量）在葡萄糖静脉内输注40分钟期间减少小于0.2单位。（30 mg/kg）在高血糖条件下（26 mM）使肿瘤pHi和pHe降低约0.4 001）和约0.6（P <0.001）单位;巧合的是，核苷三磷酸：Pi比相对于基线水平降低约60%（P < 0.004）。在肝脏中观察到对MIBG加高血糖的反应，pHi和pHe的变化极小，三磷酸核苷：Pi比值（26%，P = 0.2）略有下降。这些结果表明，在正常血糖和高血糖条件下，小的人黑素瘤异种移植物（≤ 8 mm）可能表现出相对高水平的氧化磷酸化，这可能被MIBG阻断。酸化可能是由于MIBG抑制肿瘤细胞线粒体呼吸的直接作用，或通过间接的全身作用（仍有待鉴定）导致乳酸产生增加。MIBG和高血糖的协同作用导致肿瘤的显著酸化和肿瘤生物能量状态的降低，并且与正常组织相比，该作用对肿瘤具有很大的选择性。
In vivo 31P magnetic resonance spectroscopy demonstrates that human melanoma xenografts can be significantly acidified by induction of hyperglycemia combined with administration of m-iodobenzylguanidine (MIBG), an inhibitor of mitochondrial respiration. In melanoma xenografts (< or =8 mm diameter), intracellular pH (pHi, measured by the chemical shift of the Pi resonance) and extracellular pH (pHe, measured with 3-aminopropylphosphonate) was reduced by less than 0.2 unit during i.v. infusion of glucose for 40 min. Administration of MIBG (30 mg/kg) under hyperglycemic conditions (26 mM) reduced tumor pHi and pHe by approximately 0.4 (P < 0.001) and approximately 0.6 (P < 0.001) unit, respectively; coincidentally, the nucleoside triphosphates:Pi ratio decreased approximately 60% (P < 0.004) relative to the baseline level. Minimal changes in pHi and pHe and a small decrease in nucleoside triphosphates:Pi ratio (26%, P = 0.2) were observed in liver in response to MIBG plus hyperglycemia. These results suggest that under normoglycemic and hyperglycemic conditions, small human melanoma xenografts (< or =8 mm) may exhibit a relatively high level of oxidative phosphorylation that may be blocked by MIBG. The acidification may result from increased lactate production as a direct effect of MIBG inhibition of respiration in mitochondria of tumor cells, or through indirect systemic effects, which remain to be identified. The synergetic effects of MIBG and hyperglycemia result in significant acidification of the tumor and a decrease in tumor bioenergetic status, and the effects are largely selective for tumors in comparison with normal tissues.