Universitaetsklinik fuer Neurochirurgie, University Magdeburg, Magdeburg, Germany.
Department of Neurosurgery, University Hospital of Marburg, Baldingerstr., 35033, Marburg, Germany.
J Neurooncol. 2018 Sep;139(3):573-582. doi: 10.1007/s11060-018-2918-1. Epub 2018 Jun 5.
Resveratrol and radiation decrease viability in various tumor cells. This study aims to investigate combined effects of resveratrol and radiation on viability, induction of apoptosis and necrosis, and expression of apoptosis modulators in rodent GH3 and TtT/GF pituitary adenoma cells in vitro.
Cells were incubated with 10-100 µM resveratrol. Medium and medium with ethanol served as controls. After 2 h, cells were irradiated with 0-5 Gray (Gy) and further incubated for 48-72 h. Cell viability was quantified using a hemocytometer. Cell death was assessed with an enzyme-linked immunosorbent assay (ELISA) that detects free nucleosomes in cell lysates and free nucleosomes released to the culture medium. Expression of B-cell lymphoma-2 protein (BCL-2) and BCL-2 associated Xprotein (BAX) was measured using quantitative real time-polymerase chain reaction (qRT-PCR) to analyze changes in BAX/BCL-2 ratio.
Resveratrol and irradiation with 4 Gy alone and in combination significantly decreased cell viability (p = 0.017 and less). In the ELISA, 10 μM resveratrol significantly induced apoptosis in TtT/GF cells at 0 Gy (p < 0.001), but not at 3 or 5 Gy. In the ELISA, 10 μM resveratrol significantly induced necrosis in GH3 cells at 0, 3 and 5 Gy (p < 0.001). While qRT-PCR did not demonstrate a significant effect of 10 µM resveratrol or radiation on expression of BAX or BCL-2, a significant increase in the BAX/BCL-2 ratio was found after irradiation with 5 Gy in GH3 cells (p = 0.0027).
While moderate irradiation solely led to inhibited proliferation, resveratrol induced cell death in rodent pituitary adenoma cells.
白藜芦醇和辐射会降低各种肿瘤细胞的活力。本研究旨在探讨白藜芦醇和辐射联合作用对体外培养的啮齿动物 GH3 和 TtT/GF 垂体腺瘤细胞活力、凋亡和坏死诱导以及凋亡调节剂表达的影响。
将细胞用 10-100 μM 白藜芦醇孵育。培养基和含乙醇的培养基作为对照。2 小时后，用 0-5 戈瑞（Gy）照射细胞，并进一步孵育 48-72 小时。使用血球计数器定量测定细胞活力。通过酶联免疫吸附试验（ELISA）检测细胞裂解物中的游离核小体和释放到培养基中的游离核小体来评估细胞死亡。使用定量实时聚合酶链反应（qRT-PCR）测量 B 细胞淋巴瘤-2 蛋白（BCL-2）和 BCL-2 相关 X 蛋白（BAX）的表达，以分析 BAX/BCL-2 比值的变化。
白藜芦醇和 4 Gy 单独及联合照射均显著降低细胞活力（p = 0.017 和更小）。在 ELISA 中，10 μM 白藜芦醇在 0 Gy 时显著诱导 TtT/GF 细胞凋亡（p < 0.001），但在 3 或 5 Gy 时没有。在 ELISA 中，10 μM 白藜芦醇在 0、3 和 5 Gy 时显著诱导 GH3 细胞坏死（p < 0.001）。虽然 qRT-PCR 未显示 10 μM 白藜芦醇或辐射对 BAX 或 BCL-2 表达有显著影响，但在 GH3 细胞中用 5 Gy 照射后发现 BAX/BCL-2 比值显著增加（p = 0.0027）。
虽然适度照射仅导致增殖抑制，但白藜芦醇诱导了啮齿动物垂体腺瘤细胞的细胞死亡。
