Department of Radiotherapy, The First Hospital of China Medical University, Shenyang 110001, PR China.
Oncol Rep. 2013 Jan;29(1):380-6. doi: 10.3892/or.2012.2091. Epub 2012 Oct 19.
It is crucial to enhance tumor radiosensitivity for the purpose of both lowering the dose of ionizing radiation (IR) and achieving higher antitumor efficacy. We identified curcumin as a radiosensitizer to enhance non-Hodgkin's lymphoma (NHL) cell response to IR in vitro and further investigated the mechanism mediating this effect. We treated Namalwa, Ramos and Raji cell lines with vehicle, curcumin, IR and curcumin-IR. Cell viability and cell cycle distribution were determined to ascertain the radiosensitization effect of curcumin. DNA damage-related proteins, cell cycle regulatory proteins, phosphorylation of mammalian target of rapamycin (mTOR) and the nuclear translocation of the downstream nuclear factor-κB (NF-κB) target were examined by western blotting. Treatment with curcumin led to decreased viability of all three types of NHL cells and had a profound radiosensitization effect. Pre-treatment with curcumin at a low concentration of 2 µmol/l increased IR-induced G2/M arrest in the cell cycle and increased the expression of cyclin-dependent kinase inhibitors, p21cip1 and p53. However, this effect was blocked when NHL cells were pre-treated with 10 µmol/l of KU55933, a specific inhibitor of ataxia-telangiectasia-mutated (ATM). Pre-treatment with curcumin inhibited the phosphorylation of mTOR and the nuclear translocation of the downstream NF-κB target induced by IR. Curcumin enhanced the cell response to IR in NHL mediated through the induction of G2/M phase arrest and the inhibition of both a constitutive and IR-induced activation of the mTOR-NF-κB pathway. This offers great potential for curcumin to be used in conjunction with radiotherapy for NHL in order to increase the efficiency of the treatment.
提高肿瘤放射敏感性对于降低电离辐射（IR）剂量和提高抗肿瘤疗效至关重要。我们发现姜黄素可作为放射增敏剂，增强体外非霍奇金淋巴瘤（NHL）细胞对 IR 的反应，并进一步研究了介导这种效应的机制。我们用载体、姜黄素、IR 和姜黄素-IR 处理 Namalwa、Ramos 和 Raji 细胞系。通过测定细胞活力和细胞周期分布来确定姜黄素的放射增敏作用。通过 Western blot 检测与 DNA 损伤相关的蛋白、细胞周期调节蛋白、哺乳动物雷帕霉素靶蛋白（mTOR）的磷酸化和下游核因子-κB（NF-κB）靶的核转位。用姜黄素处理可降低三种 NHL 细胞的活力，并具有显著的放射增敏作用。用 2 μmol/l 的低浓度姜黄素预处理可增加 IR 诱导的细胞周期 G2/M 期阻滞，并增加细胞周期蛋白依赖性激酶抑制剂 p21cip1 和 p53 的表达。然而，当 NHL 细胞用特定的 ATM 抑制剂 KU55933（10 μmol/l）预处理时，这种作用被阻断。姜黄素预处理可抑制 IR 诱导的 mTOR 磷酸化和下游 NF-κB 靶的核转位。姜黄素通过诱导 G2/M 期阻滞以及抑制 mTOR-NF-κB 通路的组成性和 IR 诱导激活，增强 NHL 细胞对 IR 的反应。这为姜黄素与放射治疗联合治疗 NHL 以提高治疗效率提供了巨大的潜力。
