AIM To evaluate the role of RARα gone in mediating thegrowth inhibitory effect of all-trans retinoic acid(ATRA)on gastric cancer cells.METHODS The expression levels of retinoic acidreceptors(PARs)in gastric cancer cells were detected byNorthern blot.Transient transfection and chlorophenicolacetyl transferase(CAT)assay were used to show thetranscriptional activity of β retinoic acid response element(βPARE)and AP-1 activity.Cell growth inhibition wasdetermined by MTT assay and anchorage-independentgrowth assay,respectively.Stable transfection wasperformed by the method of Lipofectamine,and the cellswere screened by G418.RESULTS ATRA could induce expression level of RARα inMGC80-3,BGC-823 and SGC-7901 cells obviously,resulting in growth inhibition of these cell lines.Aftersense RARα gone was transfected into MKN-45 cells thatexpressed rather low level of RARα and could not beinduced by ATPA,the cell growth was inhibited by ATPAmarkedly.In contrast,when antisense RARα gone wastransfected into BGC-823 cells,a little inhibitory effect byATPA was seen,compared with the parallel BGC-823cells.In transient transfection assay,ATPA effectivelyinduced transcriptional activity of βRARE in MGC80-3,BGC-823,SGC-7902 and MKN/RARα cell lines,but not inMKN-45 and BGC/aRARα cell lines.Similar results wereobserved in measuring anti-AP-1 activity by ATPA in thesecancer cell lines.CONCLUSION ATRA inhibits the growth of gastric cancercells by up-regulating the level of RARα; RARα is themajor mediator of ATRA action in gastric cancer cells;andadequate level of RARα is required for ATRA effect ongastric cancer cells.
