The effect of combination treatment with docosahexaenoic acid and 5-fluorouracil on the mRNA expression of apoptosis-related genes, including the novel gene BCL2L12, in gastric cancer cells

In Vitro Cell Dev Biol Anim. 2009 Jan-Feb;45(1-2):69-74. doi: 10.1007/s11626-008-9154-5. Epub 2008 Nov 18.

Abstract

Docosahexaenoic acid (DHA) plays an important role in suppressing the growth of cancer. In this paper, the synergetic anticancer effect of combination DHA with 5-fluorouracil (5-FU) was investigated in gastric carcinoma cells. We found that DHA inhibited the growth of cultured SGC7901 cells at different concentrations in a dose- and time-dependent manner. Furthermore, the growth-inhibition activities of increasing concentration of 5-FU were markedly enhanced when different doses of 5-FU were administered in the combination with dose as low as 40 microg/ml of DHA. The early phase of apoptosis was increased in DHA- and 5-FU-treated cells. In the case of apoptotic genes expression in the combination-treated cells, BAX mRNA expression increased, whereas FAS, BCL-2, BCL2L12, and CASPASE-9 mRNA expression decreased. These results suggest that DHA strongly enhances the anticancer effect of 5-FU. Moreover, the application of both compounds on gastric cancer cells provides a new potential approach for cancer therapy.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Docosahexaenoic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Fluorouracil / pharmacology*
  • Gene Expression Regulation, Developmental / drug effects*
  • Humans
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / physiopathology*

Substances

  • Antimetabolites, Antineoplastic
  • BCL2L12 protein, human
  • Muscle Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Docosahexaenoic Acids
  • Fluorouracil