title: Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia.
abstract: Cancer cells preferentially catalyze glucose through the glycolytic pathway in the presence of adequate oxygen. This phenomenon is known as the Warburg effect. As is the case with numerous cancer therapeutic agents, resistance remains a significant problem when using Taxol® to treat malignancies. The present study reported that expression of pyruvate dehydrogenase kinase 1 (PDK1) was induced by Taxol treatment at low toxic concentrations in oral cancer cells. In addition, Taxol‑resistant cells exhibited upregulated PDK1 protein and mRNA expression. Elevated PDK1 levels contribute to Taxol resistance under hypoxic conditions. Inhibition of PDK1 expression was observed when oral cancer cells were treated with the PDK1 inhibitor dichloroacetate (DCA). The combination of Taxol with DCA showed synergistic inhibitory effects on Taxol‑resistant cells under hypoxic conditions; these effects were not observed in Taxol‑sensitive oral cancer cells under normoxic conditions. The present study provides a novel mechanism for overcoming Taxol resistance in oral cancer cells, and will contribute towards the development of clinical therapeutics for cancer patients.
authors.affiliation: Department of Prosthodontics, School of Stomatology, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Prosthodontics, School of Stomatology, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Han-Fang
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Department of Prosthodontics, School of Stomatology, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Ying-Zi
authors.initials: YZ
authors.lastname: Guo
authors.affiliation: Department of Prosthodontics, School of Stomatology, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Peng-Yi
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Zhong-Shung
authors.initials: ZS
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics, School of Stomatology, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Hua-Dong
authors.initials: HD
authors.lastname: Gao
authors.affiliation: Department of Prosthodontics, School of Stomatology, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Xie
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004357:Drug Synergism; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase
chemical_list: D000970:Antineoplastic Agents; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D003999:Dichloroacetic Acid; D017346:Protein Serine-Threonine Kinases; D017239:Paclitaxel