Chemotherapy-induced changes in the energetics of human breast cancer cells; 31P- and 13C-NMR studies.
Chemotherapy-induced changes in the energetics of human breast cancer cells; 31P- and 13C-NMR studies.
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化疗引起的人类乳腺癌细胞能量变化；
DOI：
10.1016/0167-4889(90)90219-4
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Degani,H
中科院分区：
文献类型：
--
作者：
Neeman,M;Eldar,H;Rushkin,E;Degani,H
T47 D-克隆11人乳腺癌细胞在阿霉素和其他几种抗癌药物治疗后的早期能量学变化的特征在于31 P-和13 C-NMR光谱。用细胞毒性剂量的阿霉素（10− 5 M）、道诺霉素（10− 5 M）或放线菌素D（2 · 10− 6 M）处理细胞后，三磷酸核苷（NTP）的含量立即增加。在处理后6至8小时达到30至50%的最大增加，随后逐渐降低，与由于细胞死亡导致的细胞数量下降一致雅阁。高效液相色谱测量表明，阿霉素诱导的NTP池的建立主要是由于ATP和GTP的特定增加。用细胞毒性剂量的阿糖胞苷（10− 4 M）和顺铂（10− 4 M）以及抑制生长剂量的抗雌激素他莫昔芬（2 · 10− 6 M）处理，不会诱导NTP含量的早期增加。阿霉素和放线菌素-D没有改变显着的葡萄糖消耗率和乳酸生产通过糖酵解在第一个4至8小时的治疗。然而，这两种药物在此时间间隔内通过克雷布斯循环引起谷氨酸合成速率的50%抑制。补充流式细胞术研究表明，在4小时内的治疗与阿霉素或放线菌素D有没有可检测的变化，细胞周期分布。较长时间的治疗表明，每种药物以不同的方式影响细胞周期分布。因此，NTP的早期增加不能与特定的细胞周期分布相关联。结果表明，因此，药物的蒽环类和放线菌素型发挥类似的特异性和早期代谢诱导，这可能会影响能量状态的细胞。这种诱导可能与细胞毒性机制有关，并可能作为治疗反应的早期标志物。
The early changes in the energetics of T47D-clone 11 human breast cancer cells, following treatment with adriamycin and several other anti-cancer drugs were characterized by31P- and13C-NMR spectroscopy. Treatment of the cells with cytotoxic doses of either adriamycin (10−5M), daunomycin (10−5M) or actinomycin-D (2 · 10−6M) induced an immediate increase in the content of the nucleoside triphosphate (NTP) pool. A maximum increase of 30 to 50% was reached 6 to 8 h after treatment, and was followed by a gradual decrease, in accord with the decline in cell number due to cell death. High-performance liquid chromatography measurements indicated that the adriamycin-induced build-up of the NTP pool was mainly due to a specific increase in ATP and GTP. Treatment with cytotoxic doses of cytosine arabinofuranoside (10−4M) andcis-platin (10−4M) and with the antiestrogen tamoxifen at a dose which inhibited growth (2 · 10−6M) did not induce an early increase in the NTP content. Adriamycin and actinomycin-D did not alter significantly the rates of glucose consumption and lactate production via glycolysis during the first 4 to 8 h of treatment. Both drugs, however, caused during this time interval a 50% inhibition in the rate of glutamate synthesis via the Krebs cycle. Complementary flow cytometry studies have indicated that within 4 h of treatment with either adriamycin or actinomycin-D there is no detectable change in cell cycle distribution. Treatment for longer time periods indicated that each drug affects the cell cycle distribution in a different manner. Thus, the early increase in NTP can not be associated with a specific cell cycle distribution. The results suggest therefore that drugs of the antracycline and actinomycine type exert a similar specific and early metabolic induction which may affect the energy state of the cells. This induction may relate to the cytotoxic mechanism and could potentially serve as an early marker for response to treatment.