The effect pathway of retinoic acid through regulation of retinoic acid receptor α in gastric cancer cells

AIM To evaluate the role of RARα gone in mediating the growth inhibitory effect of all-trans retinoic acid(ATRA) on gastric cancer cells. METHODS The expression levels of retinoic acid receptors(PARs)in gastric cancer cells were detected by Northern blot.Transient transfection and chlorophenicol acetyl transferase(CAT)assay were used to show the transcriptional activity of β retinoic acid response element (βPARE)and AP-1 activity.Cell growth inhibition was determined by MTT assay and anchorage-independent growth assay,respectively.Stable transfection was performed by the method of Lipofectamine,and the cells were screened by G418. RESULTS ATRA could induce expression level of RARα in MGC80-3,BGC-823 and SGC-7901 cells obviously, resulting in growth inhibition of these cell lines.After sense RARα gone was transfected into MKN-45 cells that expressed rather low level of RARα and could not be induced by ATPA,the cell growth was inhibited by ATPA markedly.In contrast,when antisense RARα gone was transfected into BGC-823 cells,a little inhibitory effect by ATPA was seen,compared with the parallel BGC-823 cells.In transient transfection assay,ATPA effectively induced transcriptional activity of βRARE in MGC80-3, BGC-823,SGC-7902 and MKN/RARα cell lines,but not in MKN-45 and BGC/aRARα cell lines.Similar results were observed in measuring anti-AP-1 activity by ATPA in these cancer cell lines. CONCLUSION ATRA inhibits the growth of gastric cancer cells by up-regulating the level of RARα; RARα is the major mediator of ATRA action in gastric cancer cells;and adequate level of RARα is required for ATRA effect on gastric cancer cells.

AIM To evaluate the role of RARa gene in mediating the growth inhibitory effect of ail-trans retinoic acid (ATRA)on gastric cancer cells.``METHODS The expression levels of retinoic acid receptors (RARs) in gastric cancer cells were detected by Northern blot. Transient transfection and chlorophenicol acetyl transferase (CAT) assay were used to show the transcriptional activity of β retinoic acid response element (βRARE) and AP-l activity. Cell growth inhibition was determined by MTT assay and anchorage-independent growth assay, respectively. Stable transfection was performed by the method of Lipofectamine, and the cells were screened by G418.``RESULTS ATRA could induce expression level of RARα in MGC80-3, BGCC8823 and SGC-7901 cells obviously,resulting in growth inhibition of these cell lines. After sense RARa gene was transfected into MKN-45 cells that expressed rather Iow level of RARα and could not be induced by ATRA, the cell growth was inhibited by ATRA markedly. In contrast, when antisense RARα gene was transfected into BGC-825 cells, a little inhibitory effect by ATRA was seen, compared with the parallel BGC-823cells. In transient transfection assay, ATRA effectively induced transcriptional activity of βRARE in MGC80-3,BGC.823, SGC-7902 and MKN/RARa cell lines, but not in MKN-45 and BGC/aRARa cell lines. Similar results were observed in measuring anti-AP-l activity by ATRA in these cancer cell lines.``CONCLUSION ATRA inhibits the growth of gastric cancer cells by up-regulating the level of RARa; RARa is the major mediator of ATRA action in gastric cancer cells; and adequate level of RAPa is required for ATRA effect on gastric cancer cells.