title: Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer.
abstract: 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.
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, 29 Gaotanyan Street, Chongqing 400038, China.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Tong
authors.forename: Ganfeng
authors.initials: G
authors.lastname: Xie
authors.forename: Jinxia
authors.initials: J
authors.lastname: He
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.forename: Houjie
authors.initials: H
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D004357:Drug Synergism; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D003999:Dichloroacetic Acid; D017346:Protein Serine-Threonine Kinases; D053148:Caspase 3; D005472:Fluorouracil