Genistein Enhances Radiosensitivity of Human Hepatocellular Carcinoma Cells by Inducing G2/M Arrest and Apoptosis
Genistein Enhances Radiosensitivity of Human Hepatocellular Carcinoma Cells by Inducing G2/M Arrest and Apoptosis
复制标题
金雀异黄素通过诱导 G2/M 期停滞和凋亡增强人肝细胞癌细胞的放射敏感性
DOI：
10.1667/rr15380.1
复制
发表时间：
2020-03-01
影响因子：
3.4
通讯作者：
Song, Lihua
中科院分区：
文献类型：
--
作者：
Yan, Hongli;Jiang, Jing;Song, Lihua
对于根治性手术难治的局限性肝细胞癌（HCC）放射治疗患者，迫切需要新的放射增敏剂。我们以前发现，染料木黄酮，一个主要的大豆黄酮，发挥辐射防护作用的L-02正常肝细胞在低浓度。在这里，我们报道5 μM染料木黄酮对L-02细胞的伤害比HCC细胞小，并且它通过增强DNA损伤、染色体畸变和G2/M期细胞周期阻滞以及加剧凋亡而显著增强HCC细胞的放射敏感性。从机制上讲，染料木黄酮抑制了X射线诱导的磷酸化Bad（Ser 136）水平的降低，但增强了磷酸化Chk 2（Thr 68）、磷酸化ATM（Ser 1981）和γ-H2 AX的水平。基因芯片分析表明，下调POU 6 F和CCNE 2的表达，上调FBXO 32和cyclin B1的表达可能在染料木素诱导的放射敏感性中起重要作用。这些结果表明，金雀异黄素作为一个有趣的候选人肝癌的辅助放疗，并表明，金雀异黄素引起的损害比肝癌细胞正常细胞诱导G2/M期阻滞和凋亡。
New radiosensitizers are urgently needed for radiation therapy patients with localized hepatocellular carcinoma (HCC) that is refractory to radical surgery. We previously found that genistein, a major soy isoflavone, exerts radioprotective effects on L-02 normal liver cells at low concentrations. Here, we report that 5 µM genistein shows less harm to L-02 cells than HCC cells and that it significantly enhances the radiosensitivity of HCC cells by enhancing DNA damage, chromosomal aberrations and cell cycle arrest at G2/M phase and by exacerbating apoptosis. Mechanistically, genistein aggravates X-ray-induced decreases in the levels of phospho-Bad (Ser136) but enhances the levels of phospho-Chk2 (Thr68), phospho-ATM (Ser1981) and γ-H2AX. Micro-array analysis indicated that downregulation of POU6F and CCNE2 expression and upregulation of FBXO32 and cyclin B1 expression might play vital roles in genistein-induced radiosensitivity. These findings suggest genistein as an interesting candidate for adjuvant radiotherapy for HCC and indicate that genistein causes less harm to normal cells than HCC cells by inducing G2/M arrest and apoptosis.