Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer.
Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer.
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二氯乙酸联合5-氟尿嘧啶对结直肠癌的协同抗肿瘤作用
DOI：
10.1155/2011/740564
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发表时间：
2011
影响因子：
--
通讯作者：
Liang H
中科院分区：
文献类型：
--
作者：
Tong J;Xie G;He J;Li J;Pan F;Liang H
二氯乙酸酯(DCA)是一种丙酮酸脱氢酶(PDK)的抑制剂，近年来被证明是一种有前景的无毒抗肿瘤药物，可促进肿瘤细胞的凋亡。本研究旨在探讨DCA联合5-氟尿嘧啶(5-FU)对结直肠癌细胞的抑制作用。用DCA或5-FU或DCA与5-FU联合作用于4株人结直肠癌细胞。用3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium法测定细胞存活率。用中效原理评价DCA与5-FU的相互作用。用溴脱氧尿嘧啶核苷(BrdU)免疫细胞化学方法检测大肠癌细胞增殖情况。流式细胞仪检测细胞周期和细胞凋亡率，免疫印迹法检测细胞凋亡相关分子的表达。结果表明，DCA对结直肠癌细胞的生长有抑制作用，与5-FU联用具有协同抗增殖作用。此外，与5-FU单独作用相比，DCA和5-FU联合作用可促进大肠癌细胞的凋亡，表现为Bcl2、Bax和caspase-3蛋白的变化。结果提示，DCA与5-FU对体外培养的大肠癌细胞具有协同抗肿瘤作用。
Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been recently demonstrated as a promising nontoxic antineoplastic agent that promotes apoptosis of cancer cells. In the present study, we aimed to investigate the antitumor effect of DCA combined with 5-Fluorouracil (5-FU) on colorectal cancer (CRC) cells. Four human CRC cell lines were treated with DCA or 5-FU, or a combination of DCA and 5-FU. The cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The interaction between DCA and 5-FU was evaluated by the median effect principle. Immunocytochemistry with bromodeoxyuridine (BrdU) was carried out to determine the proliferation of CRC cells. Cell cycle and apoptosis were measured by flow cytometry, and the expression of apoptosis-related molecules was assessed by western blot. Our results demonstrated that DCA inhibited the viability of CRC cells and had synergistic antiproliferation in combination with 5-FU. Moreover, compared with 5-FU alone, the apoptosis of CRC cells treated with DCA and 5-FU was enhanced and demonstrated with the changes of Bcl-2, Bax, and caspase-3 proteins. Our results suggest that DCA has a synergistic antitumor effect with 5-FU on CRC cell lines in vitro.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
8.8
作者：
Michelakis, E. D.;Webster, L.;Mackey, J. R.
通讯作者：
Mackey, J. R.
影响因子：
2.8
作者：
Cao, Wengang;Yacoub, Saif;Rosser, Charles J.
通讯作者：
Rosser, Charles J.
影响因子：
64.8
作者：
Reed, JC
通讯作者：
Reed, JC
影响因子：
8.4
作者：
Tebbutt, NC;Cattell, E;Kerr, D
通讯作者：
Kerr, D