Objective   The aim of this in vitro study is to assess the reversing effects of arsenic trioxide(As₂O₃) on multi-drug-resistance(MDR) of SGC7901/adriamycin(ADM) and determine the molecular mechanism associated with Ras/p-ERK downregulation in human gastric cancer cells.

  Methods   The reversing effects of As₂O₃ before and after the treatment with an ERK agonist were determined by methyl thiazolyl tetrazolium assay.The molecular mechanism involved was further studied by examining the expressions of Ras and phosphorylated p-ERK by immunocytochemical assay.The process was repeated in pre-and post-intervention of As₂O₃ and granulocyte colony stimulating factor(G-CSF), respectively.Changes in the cell cycle and apoptotic rates were determined by flow cytometry.

  Results   SGC7901/ADM was resistant to ADM, and As₂O₃ could reverse the drug resistance.After the treatment of As₂O₃ at a dose of 0.5 μmol/L for 48 h, the the multiple of reversed drug resistance was about 6.29 approximately, which was greater compared with that of the normal cells.After administration of As₂O₃, the IC50decreased dramatically, which shows that As₂O₃ could reverse MDR.After the G-CSF intervention, the multiple of the reversing effects was only 4.72.Immunocytochemical assay showed higher expressions of Ras in SGC7901/ADM than in the parental cell line SGC7901/S.No obvious difference in the p-ERK expressions of these cell lines was observed. As₂O₃ could decrease both Ras and p-ERK expressions(q-test, P < 0.01).After pre-treatment with the ERK agonist, Ras and p-ERK expressions decreased(t-test, P < 0.01).Flow cytometry indicated that the proportion of G₀-G₁ cells and apoptosis rate were higher in the As₂O₃ –treated group(0.1 and 0.5 μmol/L) than in the control groups.And apoptotic rate of both the cells significantly decreased in the As₂O₃ group of the same dose after treatment of G-CSF.

  Conclusion   As₂O₃ can reduce the MDR of gastric cancer in vitro via the Ras/p-ERK signaling transduction pathway.