对乙酰氨基酚对不同脑胶质瘤细胞的放射增敏作用及其机制研究

目的 探讨对乙酰氨基酚联合放射对人恶性脑胶质瘤细胞2种细胞的放射增敏效应及其可能的机制。 方法 以人恶性脑胶质瘤细胞株SHG-44及其接受10Gy 6MV X射线照射后的存活后代细胞SHG-44_10Gy为研究对象,采用免疫细胞化学和RT-PCR检测2株细胞COX-2的表达,集落形成实验测定对乙酰氨基酚对细胞的放射增敏作用。结果 HG-44_10Gy较SHG-44的放射敏感性低(P<0.01);免疫细胞化学染色SHG-44和SHG-44_10Gy细胞的胞质及胞膜均有COX-2蛋白的表达,且后者明显高于前者;RT-PCR检测SHG-44_10Gy中COX-2 mRNA表达水平明显高于SHG-44细胞,与放射敏感性有显著的相关性(r=0.976,P<0.01);对乙酰氨基酚联合放疗分别作用于SHG-44和SHG-44_10Gy细胞,与单纯照射组相比,显示了放射增敏作用,SHG-44细胞D₀值和D_q值增敏比分别为1.09和1.11,SHG-44_10Gy的SER分别为1.12和3.01。结论 人恶性脑胶质瘤细胞株SHG-44及其照射存活后代细胞均有COX-2表达,且对辐射耐受的存活后代细胞中COX-2明显增高;对乙酰氨基酚可通过抑制COX-2的表达增加人脑胶质瘤SHG-44细胞尤其是其照射后代细胞的放射敏感性。

Radiosensitization of acetaminophen on human glioma cell lines and its mechanism

Objective To investigate the radiosensitivity enhancement and underlying mechanism of acetaminophen ,non-selective cyclooxygenase (COX)-2 inhibitor, on human glioma cell lines expressing differential COX-2 levels. Methods The SHG-44 cells were irradiated with a dose of 10 Gy using 6MV X-rays generated by linar accelerator. The progeny of the cells were cultured and named SHG-44_10Gy. COX-2 mRNA and protein expression of SHG-44 and SHG-44_10Gy were detected by RT-PCR and immunocytochemisty staining. Clongenic assay was used for radiation survival experiment. Results The declined radiosensitivity was detected in the SHG-44_10Gy. RT-PCR showed that the expression of COX-2 mRNA in SHG-44_10Gy significantly higher than that in SHG-44 cells (P<0.01). The cell inhibition induced by Acetaminophen and irradiation was positively correlated with the expression of COX-2 mRNA(P<0.01). was observed from the dose-survival curve and the related parameters. The values of SER were 1.09(D₀) or 1.11(D_q)in SHG-44 cells and 1.12(D₀)or 3.01(D_q)in SHG-44_10Gy. Conclusions SHG-44_10Gy cells are more radio-resistant, and one of the fundamental mechanisms might be the upregulation of COX-2 expression in protein and mRNA levels. Acetaminophen could enhance the radisensitivity of glioma cells, especially the surviving progeny from the irradiated SHG-44 cells.