Guggulsterone-mediated enhancement of radiosensitivity in human tumor cell lines.
Guggulsterone-mediated enhancement of radiosensitivity in human tumor cell lines.
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DOI：
10.3389/fonc.2011.00019
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发表时间：
2011
影响因子：
4.7
通讯作者：
Cook JA
中科院分区：
文献类型：
--
作者：
Choudhuri R;Degraff W;Gamson J;Mitchell JB;Cook JA
目的：观察银杏甾酮（GS）对人癌细胞辐射反应的影响。材料与方法：通过细胞存活率测定、细胞生长测定、NF-κB活性测定、几种关键促生长受体的蛋白质印迹、DNA修复蛋白γ H2 AX和流式细胞术DNA分析，观察GS对肿瘤细胞的辐射效应。结果如下：GS抑制辐射诱导的NF-κB活化，增强胰腺癌细胞系PC-Sw的辐射敏感性，降低细胞周期运动和细胞生长。GS可降低MCF 7细胞ERα蛋白和结肠癌、胰腺癌细胞IGF 1-Rβ蛋白的表达，抑制辐射后DNA双链断裂（DSB）修复。结论：GS诱导的辐射增敏可能是由于几种不同的机制，包括抑制NF-κB活化和减少IGF 1-Rβ。此外，GS诱导γ H_2AX的形成，主要在S期，表明S期的DNA DSB可能是GS诱导辐射敏感性的另一个原因。GS可下调ERα表达，提示GS可用于治疗对他莫昔芬耐药的雌激素阳性肿瘤。
Purpose: To observe the effect of guggulsterone (GS) on the radiation response in human cancer cell lines. Materials and methods: The radiation response of cancer cells treated with GS was observed by cell survival studies, cell growth assay, NF-κB activity assay, western blotting of some key growth promoting receptors, the DNA repair protein γH2AX, and flow cytometry for DNA analyses. Results: GS inhibited radiation induced NF-κB activation and enhanced radiosensitivity in the pancreatic cell line, PC-Sw. It reduced both cell cycle movement and cell growth. GS reduced ERα protein in MCF7 cells and IGF1-Rβ protein in colon cancer cells and pancreatic cancer cells and inhibited DNA double strand break (DSB) repair following radiation. Conclusion: GS induced radiation sensitization may be due to several different mechanisms including the inhibition of NF-κB activation and reductions in IGF1-Rβ. In addition, GS induced γH2AX formation, primarily in the S-phase, indicates that DNA DSB's in the S-phase may be another reason for GS induced radiosensitivity. ERα down-regulation in response to GS suggests that it can be of potential use in the treatment of estrogen positive tumors that are resistant to tamoxifen.