DCA increases the antitumor effects of capecitabine in a mouse B16 melanoma allograft and a human non-small cell lung cancer A549 xenograft

Cancer Chemother Pharmacol. 2013 Nov;72(5):1031-41. doi: 10.1007/s00280-013-2281-z. Epub 2013 Sep 17.

Abstract

Purpose: Capecitabine is one of the few chemotherapy drugs with high oral availability. Recently, sodium dichloroacetate (DCA) has shown great potential as an anticancer agent. In the present study, we assessed the anticancer effect of DCA in combination with capecitabine for cancers that modestly expressed TP.

Methods: A mouse B16 melanoma allograft and a human non-small cell lung cancer A549 xenograft were used to assess the effect of DCA and capecitabine combined treatment. Histology and immunohistochemistry were used to detect the apoptosis and proliferation of cancer cells. Real-time PCR and Western blot were carried out to detect the expression of TP and caspases, respectively.

Results: For the first time, we report that DCA increased the antitumor effects of capecitabine in a mouse B16 allograft and a human A549 xenograft by promoting apoptosis of tumor cells. DCA has little effect on the expression of TP.

Conclusions: Our finding suggests that DCA in combination with capecitabine might be potential as a new therapeutic regimen against some cancers.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Dichloroacetic Acid / administration & dosage
  • Dichloroacetic Acid / adverse effects
  • Dichloroacetic Acid / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives*
  • Fluorouracil / therapeutic use
  • Humans
  • Male
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasm Proteins / metabolism
  • Prodrugs / administration & dosage
  • Prodrugs / adverse effects
  • Prodrugs / therapeutic use*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Random Allocation
  • Thymidine Phosphorylase / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antimetabolites, Antineoplastic
  • Neoplasm Proteins
  • Prodrugs
  • Protein Kinase Inhibitors
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Deoxycytidine
  • Capecitabine
  • Dichloroacetic Acid
  • Thymidine Phosphorylase
  • Protein Serine-Threonine Kinases
  • Fluorouracil