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Conditioned media from solid tumor cell lines treated with retinoic acids both decreases and increases proliferation of capillary endothelial cells.

机译:来自视黄酸处理的实体肿瘤细胞系的条件培养基既减少又增加了毛细血管内皮细胞的增殖。

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These studies investigated the effects of retinoic acids on endothelial cell proliferation. Three human neoplastic cell lines, U-373 MG glioblastoma, DU-145 prostate carcinoma, and TCCSUP bladder transitional cell carcinoma, were treated with all-trans, 9-cis, or 13-cis retinoic acids at 0.0001 to 10 microM. Hypoxia was used to ensure the expression of the angiogenic phenotype. Conditioned media (CM) were prepared by hypoxic culturing of the tumor cells with retinoic acids for 24 hours. Then CM were transferred to bovine capillary endothelial cells for 48 hours of normoxic culturing, counted and compared to controls. CM from U-373 MG and DU-145 cells, but not TCCSUP cells, treated with all-trans or 9-cis retinoic acids at several concentrations below 1 microM, caused significant (P<0.05) increases in endothelial cell proliferation of between 13 to 18%. Both nonconditioned and conditioned media, for retinoic acid concentrations above 1 microM, inhibited endothelial cell proliferation. All CM for 13-cis retinoic acid decreased endothelial cell proliferation. These results show that the cytotoxicity of retinoic acids and the growth promoting/inhibiting ability of the conditioned media is retinoic acid isoform, time, concentration, and cell type dependent. Most importantly, the conditioned media from tumor cells treated with low concentrations of all-trans or 9-cis retinoic acids significantly increased endothelial cell proliferation.
机译:这些研究调查了视黄酸对内皮细胞增殖的影响。用0.0001至10 microM的全反式,9-顺式或13-顺式视黄酸处理三种人类肿瘤细胞系U-373 MG胶质母细胞瘤,DU-145前列腺癌和TCCSUP膀胱移行细胞癌。缺氧用于确保血管生成表型的表达。通过用视黄酸对肿瘤细胞进行低氧培养24小时来制备条件培养基(CM)。然后将CM转移到牛毛细血管内皮细胞中进行常氧培养48小时,计数并与对照进行比较。来自U-373 MG和DU-145细胞的CM,而非TCCSUP细胞,经全反式或9-顺式视黄酸以低于1 microM的几种浓度处理后,导致内皮细胞增殖显着(P <0.05)增加至13之间至18%。对于视黄酸浓度高于1 microM的非条件培养基和条件培养基,均会抑制内皮细胞的增殖。所有CM为13-顺式视黄酸均降低了内皮细胞的增殖。这些结果表明视黄酸的细胞毒性和条件培养基的生长促进/抑制能力取决于视黄酸的同工型,时间,浓度和细胞类型。最重要的是,用低浓度的全反式或9-顺式视黄酸处理的肿瘤细胞产生的条件培养基显着增加了内皮细胞的增殖。

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