Department of Radiotherapy, the First Hospital of China Medical University, China.
J Pharmacol Sci. 2013;121(4):247-56. doi: 10.1254/jphs.12149fp.
The phosphatidylinositol-3-kinase (PI3K) / protein kinase B (AKT) signal transduction pathway is commonly misregulated in lymphoma and associated with tumorigenesis and enhanced resistance to radiotherapy. Curcumin has been shown to inhibit the PI3K/AKT signal transduction pathway in several tumor models. In this study, we found that curcumin inhibits constitutive and radiation-induced expression of the PI3K/AKT pathway and its downstream regulator nuclear factor kappaB (NF-κB) in human Burkitt's lymphoma, a high-grade non-Hodgkin's lymphoma (NHL). We further demonstrated that the blockage of radiation-induced activation of the PI3K/AKT pathway and its downstream regulator NF-κB by either curcumin or specific PI3/AKT inhibitors (LY294002 for PI3K or SH-5 for AKT) enhance apoptosis in three human Burkitt's lymphoma cell lines (Namalwa, Ramos, and Raji) that were treated with ionizing radiation. However, no synergic effect on radiation-induced apoptosis was found in the cells co-pretreated with curcumin combined with LY294002 or curcumin combined with SH-5. The results from this study suggest that curcumin might play an important role in radiotherapy of high-grade NHL through inhibition of the PI3K/AKT-dependent NF-κB pathway.
磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶 B（AKT）信号转导通路在淋巴瘤中经常失调，与肿瘤发生和对放射治疗的抵抗力增强有关。姜黄素已被证明可抑制几种肿瘤模型中的 PI3K/AKT 信号转导通路。在这项研究中，我们发现姜黄素可抑制人伯基特淋巴瘤（一种高级非霍奇金淋巴瘤（NHL））中 PI3K/AKT 通路及其下游调节因子核因子 kappaB（NF-κB）的组成性和辐射诱导表达。我们进一步证明，通过姜黄素或特定的 PI3/AKT 抑制剂（LY294002 用于 PI3K 或 SH-5 用于 AKT）阻断辐射诱导的 PI3K/AKT 通路及其下游调节因子 NF-κB 的激活可增强三种人伯基特淋巴瘤细胞系（Namalwa、Ramos 和 Raji）在接受电离辐射后的细胞凋亡。然而，在用姜黄素联合 LY294002 或姜黄素联合 SH-5 预处理的细胞中，未发现对辐射诱导的细胞凋亡有协同作用。本研究结果表明，姜黄素可能通过抑制 PI3K/AKT 依赖性 NF-κB 通路在高级 NHL 的放射治疗中发挥重要作用。
