All-trans retinoic acid modulates fas expression and enhances chemosensitivity of human medulloblastoma cells.
All-trans retinoic acid modulates fas expression and enhances chemosensitivity of human medulloblastoma cells.
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DOI：
10.3892/ijmm.5.2.145
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发表时间：
2000-02
影响因子：
5.4
通讯作者：
J. Liu;L. Guo;L. Jun-wei;N. Liu;H. Li
中科院分区：
文献类型：
--
作者：
J. Liu;L. Guo;L. Jun-wei;N. Liu;H. Li
维甲酸(RA)能促进人髓母细胞瘤细胞Med-3分化，但不足以诱导细胞死亡，提示其对髓母细胞瘤的作用有限。另一方面，分化的肿瘤细胞被认为对化疗药物更敏感。为了阐明这种作用于髓母细胞瘤细胞的可能性，本研究用10微米/L维甲酸、1.0微克/毫升顺铂(CP)及其半量组合处理Med-3细胞，观察其对细胞增殖、形态和死亡模式的影响。免疫细胞化学染色和Western印迹杂交分析Fas及其配体(FasL)的表达。用抗Fas抗体孵育经10µm/L RA或1.0µg/mlCP处理的Med-3细胞。结果表明，RA和CP对细胞生长有抑制作用，但很少诱导细胞凋亡。维甲酸和环磷酰胺各半剂量联合应用，可有效地使大部分肿瘤细胞在6d内死亡。在Med-3细胞中检测到29 kDa和37 kDa的FasL分子。在正常培养细胞和CP处理的细胞中，Fas分子分布在约30 kDa的胞浆中。10微米/L维甲酸和5微米/L维甲酸+0.5微克/毫升CP处理的细胞均可观察到另一条45 kDa的Fas条带，并出现细胞表面标记。抗Fas抗体仅能有效地诱导维甲酸处理的细胞群体的细胞凋亡。因此，我们的数据表明，RA可能通过调节Fas的表达模式来增强人髓母细胞瘤Med-3细胞的化疗敏感性。RA/CP联合方案是治疗髓母细胞瘤的一种有潜力的方法。
Retinoic acid (RA) can promote human medulloblastoma cells Med-3 toward differentiation but is not sufficient to induce cell death, suggesting its limited effect on medulloblastomas. On the other hand, the differentiated tumour cells have been supposed to be more sensitive to chemotherapeutic drugs. To elucidate this possibility for medulloblastoma cells, 10 microM/l RA, 1.0 microg/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 expressions 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 microM/l RA or 1.0 microg/ml CP. It was revealed that RA and CP could inhibit cell growth but rarely induce apoptosis. Combination of half doses each of RA and CP effectively caused most of tumour cells to die of apoptosis within 6 days. FasL molecules in 29 kDa and 37 kDa were detected in Med-3 cells with and without the treatments. The Fas molecule around 30 kDa and located in the cytoplasm was found in the normally cultured cells and the cells treated by CP. An additional 45 kDa Fas band with the appearance of its cell surface labeling was detected in the cells treated by 10 microM/l RA and by 5 microM/l RA + 0.5 microg/ml CP. The anti-Fas antibody could efficiently induce apoptosis only in the cell populations pretreated by RA. Our data thus suggest that RA can enhance the chemosensitivity of human medulloblastoma Med-3 cells presumably via modulating the Fas expression pattern. The RA/CP combined regimen would be a potential therapeutic approach for medulloblastomas.