All-trans retinoic acid modulates Fas expression and enhances chemosensitivity of human medulloblastoma cells

Retinoic acid (RA) can promote human medulloblastoma cells Med-3 toward dif ferentiation but is not sufficient to induce cell death, suggesting its lim ited effect on medulloblastomas. On the other hand, the differentiated tumo ur cells have been supposed to be more sensitive to chemotherapeutic drugs. To elucidate this possibility for medulloblastoma cells, 10 mu M/l RA, 1.0 mu g/ml cisplatin (CP) and their half-dosage combinations were utilized in this study to treat Med-3 cells and their influences in cell proliferation , morphology and death patterns were evaluated. In parallel, the expression s of Fas and its ligand (FasL) were analyzed by immunocytochemical staining and Western blot hybridization. Anti-Fas antibody was used to incubate the Med-3 cells pretreated by 10 mu M/l RA or 1.0 mu g/ml CP. It was revealed that RA and CP could inhibit cell growth but rarely induce apoptosis. Combi nation of half doses each of RA and CP effectively caused most of tumour ce lls to die of apoptosis within 6 days. Fast molecules in 29 kDa and 37 kDa were detected in Med-3 cells with and without the treatments. The Fas molec ule around 30 kDa and located in the cytoplasm was found in the normally cu ltured cells and the cells treated by CP. An additional 45 kDa Fas band wit h the appearance of its cell surface labeling was detected in the cells tre ated by 10 mu M/l RA and by 5 mu M/l RA + 0.5 mu g/ml CP. The anti-Fas anti body could efficiently induce apoptosis only in the cell populations pretre ated by RA. Our data thus suggest that RA can enhance the chemosensitivity of human medulloblastoma Med-3 cells presumably via modulating the Fas expr ession pattern. The RA/CP combined regimen would be a potential therapeutic approach for medulloblastomas.