The role of AP-1 in the upregulation of the multidrug resistance gene MDR1 in a drug-resistant gastric carcinoma cell line

Objective: To investigate the role of the multi-drug resistance gene MDR1 in the Doxorubicin-resistant SGC7901/ADR gastric adenocarcinoma cell line. Methods: We used the MTT assay to determine the cell survival rate of SGC7901 human gastric carcinoma cells and Doxorubicin-resistant SGC7901/ADR cells after treatment with three kinds of commonly used chemotherapeutic drugs. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to detect the mRNA level of mdr1 and c-Jun in SGC7901 and SGC7901/ADR cells. Transcription factor AP-1 was transfected into SGC7901 and SGC7901/ADR cells, and the transcription activity was assayed by a dual-luciferase reporter assay. The protein expression of P-gp and c-Jun was detected by Western blot. Results: The survival rate of SGC7901/ADR cells was significantly higher than that of SGC7901 cells. The mRNA level of mdr1 and c-Jun was significantly higher in SGC7901/ADR cells than in SGC7901 cells. The transcription activity of transcription factor AP-1 was different between the two cell lines. The levels of P-gp and c-Jun were higher in SGC7901/ADR cells. Conclusion: In the SGC7901/ADR cell line, multiple-drug resistance is increased and an upregulation of the MDR1 gene is observed. In gastric cancer, the activity of transcription factor AP-1 is related to the MDR of cancer cells. The expression of AP-1 may be involved in the mechanism of Doxorubicin resistance in gastric carcinoma cells.