2-Deoxy-d-Glucose Can Complement Doxorubicin and Sorafenib to Suppress the Growth of Papillary Thyroid Carcinoma Cells.
2-Deoxy-d-Glucose Can Complement Doxorubicin and Sorafenib to Suppress the Growth of Papillary Thyroid Carcinoma Cells.
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DOI：
10.1371/journal.pone.0130959
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chuang JH
中科院分区：
文献类型：
--
作者：
Wang SY;Wei YH;Shieh DB;Lin LL;Cheng SP;Wang PW;Chuang JH
肿瘤细胞的能量代谢表现出从氧化磷酸化到有氧糖酵解的转变。甲状腺乳头状癌(PTC)的一个亚型对手术和放射性碘消融术是无效的。阿霉素和索拉非尼是治疗晚期甲状腺癌的首选药物，但都会产生不良反应。在这项研究中，我们评估了2-脱氧-d-葡萄糖(2-DG)单独以及与阿霉素或索拉非尼合用对存在BRAFV600E突变(BCPAP)和不存在BRAFV600E突变(CG3)的PTC细胞的抗癌活性。与CG3细胞相比，bCPAP细胞具有更强的糖酵解能力，其胞外L乳酸产量较高，细胞内三磷酸腺苷水平较低，耗氧速率较低，与胞外酸化速率的比值较低。然而，经2-DG处理后，细胞存活率、细胞内三磷酸腺苷耗竭和细胞外L-乳酸生成均呈剂量依赖性下降。回归分析表明，两种细胞系的细胞生长均依赖于ATP的生成。2-DG增加bCPAP和CG3细胞对阿霉素和索拉非尼的化疗敏感性。这些结果表明，无论BRAFV600E突变如何，低剂量2-DG联合阿霉素或索拉非尼对PTC细胞株的治疗效果与大剂量阿霉素或索拉非尼单独作用相似。
Tumor cells display a shift in energy metabolism from oxidative phosphorylation to aerobic glycolysis. A subset of papillary thyroid carcinoma (PTC) is refractory to surgery and radioactive iodine ablation. Doxorubicin and sorafenib are the drugs of choice for treating advanced thyroid cancer but both induce adverse effects. In this study, we assessed the anti-cancer activity of 2-deoxy-d-glucose (2-DG) alone and in combination with doxorubicin or sorafenib in PTC cell lines with (BCPAP) and without (CG3) the BRAFV600E mutation. BCPAP cells were more glycolytic than CG3 cells, as evidenced by their higher extracellular l-lactate production, lower intracellular ATP level, lower oxygen consumption rate (OCR), and lower ratio of OCR/extracellular acidification rate. However, dose-dependent reduction in cell viability, intracellular ATP depletion, and extracellular l-lactate production were observed after 2-DG treatment. Regression analysis showed that cell growth in both cell lines was dependent on ATP generation. 2-DG increased the chemosensitivity of BCPAP and CG3 cell lines to doxorubicin and sorafenib. These results demonstrate that the therapeutic effects of low combined doses of 2-DG and doxorubicin or sorafenib are similar to those of high doses of doxorubicin or sorafenib alone in PTC cell lines regardless of the BRAFV600E mutation.
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影响因子：
8.8
作者：
Cheng, G.;Zielonka, J.;McAllister, D.;Tsai, S.;Dwinell, M. B.;Kalyanaraman, B.
通讯作者：
Kalyanaraman, B.
影响因子：
168.9
作者：
Brose, Marcia S.;Nutting, Christopher M.;Jarzab, Barbara;Elisei, Rossella;Siena, Salvatore;Bastholt, Lars;de la Fouchardiere, Christelle;Pacini, Furio;Paschke, Ralf;Shong, Young Kee;Sherman, Steven I.;Smit, Johannes W. A.;Chung, John;Kappeler, Christian;Pena, Carol;Molnar, Istvan;Schlumberger, Martin J.
通讯作者：
Schlumberger, Martin J.
影响因子：
5.9
作者：
MAZZAFERRI, EL;JHIANG, SM
通讯作者：
JHIANG, SM
DOI：
10.3791/2511
发表时间：
2010-12-06
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Nicholls, David G;Darley-Usmar, Victor M;Ferrick, David A
通讯作者：
Ferrick, David A
影响因子：
1.3
作者：
Farooque, Abdullah;Afrin, Farhat;Dwarakanath, B. S.
通讯作者：
Dwarakanath, B. S.