Xu Xiao, Cheng Yan, Yang Zeyu, Yin Yong, Qian Yonghong, Yang Haiyu, Zhu Shusheng, Tian Hu, Zhuang Yanshuang, Zhu Shimin, Yang Pingjin, Qin Songbing, Shen Weigan
Department of Radiotherapy, Taizhou Affiliated Hospital of Nanjing University of Chinese Medicine, Taizhou 225300, Jiangsu, China; Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
School of Computer Science and Engineering, Taizhou Institute of Science & Technology, Taizhou 225300, Jiangsu, China.
Int Immunopharmacol. 2025 Jun 5;157:114740. doi: 10.1016/j.intimp.2025.114740. Epub 2025 May 2.
To investigate whether wogonin increases the radiosensitivity of hepatocellular carcinoma (HCC) cells by activating Hippo-Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling.
HCC cells were treated with irradiation and wogonin; their proliferation and apoptosis were evaluated. Xenograft models were established to assess the radio-synergistic effects of wogonin; we evaluated whether wogonin influences the efficacy of radiotherapy in HCC cells by activating Hippo-YAP/TAZ signaling.
Fifty micromolar wogonin enhanced the radiosensitivity of HCC cells; 4-Gy X-rays promoted apoptosis in HCC cells. Wogonin pretreatment significantly increased radiosensitivity. In xenograft models, tumor weight and volume in the 100 mg/kg wogonin plus irradiation group were significantly reduced; pYAP and pTAZ levels were downregulated in HCC cells treated with radiotherapy. Following treatment with 4-Gy X-rays and 100 μM wogonin, the relative pYAP/total YAP and pTAZ/total TAZ ratios increased. We identified the possible target genes of YAP/TAZ: AXL, CCN1, and CCN2. WB results revealed the upregulation of AXL, CCN1, and CCN2 in the irradiation group. However, in the group receiving irradiation and wogonin, the protein expression levels of AXL, CCN1, and CCN2 were downregulated. XMU-MP-1 inhibited pYAP and pTAZ expression in the combination treatment group, thereby promoting AXL, CCN1, and CCN2 expression. The proliferative ability of HCC cells in the wogonin plus irradiation group was partially recovered following treatment with XMU-MP-1. Apoptosis in HCC cells was reversed after pretreatment with 2 μM XMU-MP-1 in the wogonin plus irradiation group.
Wogonin may modulate Hippo-YAP/TAZ signaling and enhance the radiosensitivity of HCCs.
研究汉黄芩素是否通过激活Hippo-Yes相关蛋白（YAP）/含PDZ结合基序的转录共激活因子（TAZ）信号通路来提高肝癌（HCC）细胞的放射敏感性。
用辐射和汉黄芩素处理肝癌细胞；评估其增殖和凋亡情况。建立异种移植模型以评估汉黄芩素的放射协同作用；我们通过激活Hippo-YAP/TAZ信号通路来评估汉黄芩素是否影响肝癌细胞的放射治疗效果。
50微摩尔的汉黄芩素增强了肝癌细胞的放射敏感性；4 Gy的X射线促进了肝癌细胞的凋亡。汉黄芩素预处理显著提高了放射敏感性。在异种移植模型中，100 mg/kg汉黄芩素加辐射组的肿瘤重量和体积显著降低；放射治疗的肝癌细胞中pYAP和pTAZ水平下调。用4 Gy X射线和100 μM汉黄芩素处理后，相对pYAP/总YAP和pTAZ/总TAZ比值增加。我们确定了YAP/TAZ的可能靶基因：AXL、CCN1和CCN2。蛋白质印迹结果显示辐射组中AXL、CCN1和CCN2上调。然而，在接受辐射和汉黄芩素的组中，AXL、CCN1和CCN2的蛋白表达水平下调。XMU-MP-1在联合治疗组中抑制pYAP和pTAZ表达，从而促进AXL、CCN1和CCN2表达。用XMU-MP-1处理后，汉黄芩素加辐射组中肝癌细胞的增殖能力部分恢复。在汉黄芩素加辐射组中，用2 μM XMU-MP-1预处理后，肝癌细胞的凋亡得到逆转。
汉黄芩素可能调节Hippo-YAP/TAZ信号通路并增强肝癌的放射敏感性。
