Tong Jingtao, Xie Ganfeng, He Jinxia, Li Jianjun, Pan Feng, Liang Houjie
Department of Oncology, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China.
J Biomed Biotechnol. 2011;2011:740564. doi: 10.1155/2011/740564. Epub 2011 Feb 20.
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.
二氯乙酸（DCA）是丙酮酸脱氢酶激酶（PDK）的抑制剂，最近已被证明是一种有前景的无毒抗肿瘤药物，可促进癌细胞凋亡。在本研究中，我们旨在研究DCA联合5-氟尿嘧啶（5-FU）对结直肠癌（CRC）细胞的抗肿瘤作用。用DCA或5-FU或DCA与5-FU的组合处理四种人CRC细胞系。通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐法测定细胞活力。根据中位效应原理评估DCA与5-FU之间的相互作用。进行溴脱氧尿苷（BrdU）免疫细胞化学以确定CRC细胞的增殖。通过流式细胞术测量细胞周期和凋亡，并通过蛋白质印迹法评估凋亡相关分子的表达。我们的结果表明，DCA抑制CRC细胞的活力，并与5-FU联合具有协同抗增殖作用。此外，与单独使用5-FU相比，用DCA和5-FU处理的CRC细胞的凋亡增强，并通过Bcl-2、Bax和caspase-3蛋白的变化得到证实。我们的结果表明，DCA在体外对CRC细胞系与5-FU具有协同抗肿瘤作用。
