Severe hypoxia of ascites and increased 18F-FDG uptake in ascites carcinomas: A paradox to Warburg effect

腹水 瓦博格效应 厌氧糖酵解 缺氧(环境) 糖酵解 艾氏腹水癌 病理 癌症 癌 医学 癌症研究 内科学 化学 新陈代谢 氧气 肿瘤细胞 有机化学
作者
Xiao‐Feng Li,A. Cahid Civelek
摘要

1137 Objectives Warburg reported his discovery that in the presence of ample oxygen (21% or 150 mmHg O2), cancer cells utilize glucose by “aerobic glycolysis” in Ehrlich ascites carcinoma model, that is Warburg effect. since the presence of hypoxia, partial oxygen pressure (pO2) Methods Ascites carcinoma (floating single cells or clusters) and peritoneal tumors (attached to serosa) were induced by HT29, A549 or MDA-MB-231 cancer cells in the mouse peritoneal cavity. pO2 of ascites was measured using OxyLite systems in ketamine anesthetized mice. 18F-FDG and hypoxia marker pimonidazole (PIMO) was administrated and their distributions were assessed by autoradiography and immunohistochemistry. Effect of carbogen breathing (95% O2 & 5% CO2) on 18F-FDG uptake was examined. Results The median pO2 of ascites was 0.90 mmHg (0.5% O2). Ascites carcinomas stained positive for PIMO indicting presence of severe hypoxia, and they had elevated 18F-FDG activity. 18F-FDG uptake was significantly higher in Conclusions In mice, ascites and ascites carcinoma are severely hypoxic. Glucose utilization measured by 18F-FDG autoradiograph is increased in hypoxic cancer cells, but not as much in oxygenated cancer cells, which might be explained by anaerobic glycolysis pathway rather than “aerobic glycolysis” of glucose metabolism, thus a challenge for conventional Warburg effect theory. Research Support Supported by Kentucky Lung Cancer Research program to XFL

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