The effect pathway of retinoic acid through regulation of retinoic acid receptor alpha in gastric cancer cells
- 生命科学－已发表论文 
AIM To evaluate the role of RAR alpha gene in mediating the growth inhibitory effect of all-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 P retinoic acid response element (beta RARE) 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 RAR alpha in MGC80-3, BGC-823 and SGC-7901 cells obviously, resulting in growth inhibition of these cell lines. After sense RAR alpha: gene was transfected into MKN-45 cells that expressed rather low level of RAR alpha and could not be induced by ATRA, the cell growth was inhibited by ATRA markedly. In contrast, when antisense RAR alpha gene was transfected into BGC-823 cells, a little inhibitory effect by ATRA was seen, compared with the parallel BGC-823 cells. In transient transfection assay, ATRA effectively induced transcriptional activity of beta RARE in MGC80-3, BGC-823, SGC-7902 and MKN/ RAR alpha cell lines, but not in MKN-45 and BGC/ aRAR alpha cell lines. Similar results were observed in measuring anti-AP-1 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 RARa is required for ATRA effect on gastric cancer cells.