Wogonin potentiates the irradiation effect on hepatocellular carcinoma by activating the Hippo-Yes-associated protein/transcriptional co-activator with PDZ-binding motif pathway

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-05-02 DOI:10.1016/j.intimp.2025.114740

Xiao Xu , Yan Cheng , Zeyu Yang , Yong Yin , Yonghong Qian , Haiyu Yang , Shusheng Zhu , Hu Tian , Yanshuang Zhuang , Shimin Zhu , Pingjin Yang , Songbing Qin , Weigan Shen

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引用次数: 0

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusion

Wogonin may modulate Hippo-YAP/TAZ signaling and enhance the radiosensitivity of HCCs.

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Wogonin通过激活具有pdz结合基序通路的希波- yes相关蛋白/转录共激活因子，增强了对肝细胞癌的照射作用

目的探讨wogonin是否通过激活hppo - yes相关蛋白(YAP)/带pdz结合基序（TAZ）信号的转录共激活因子（transcriptional co-activator）而增加肝细胞癌（HCC）细胞的放射敏感性。方法对shcc细胞进行辐照和沃戈宁处理；观察细胞的增殖和凋亡情况。建立异种移植物模型，评估沃戈宁的放射增效作用；我们通过激活希波- yap /TAZ信号来评估沃戈素是否影响肝癌细胞放疗的疗效。结果50微摩尔沃戈宁增强了肝癌细胞的放射敏感性；4-Gy x射线促进HCC细胞凋亡。Wogonin预处理显著提高放射敏感性。在异种移植瘤模型中，100 mg/kg沃戈宁加照射组肿瘤重量和体积显著降低；放疗后肝癌细胞中pYAP和pTAZ水平下调。4-Gy x射线和100 μM wogonin处理后，pYAP/总YAP和pTAZ/总TAZ比值增加。我们确定了YAP/TAZ可能的靶基因：AXL、CCN1和CCN2。WB结果显示，照射组AXL、CCN1、CCN2表达上调。而在放疗组和wogonin组，AXL、CCN1、CCN2蛋白表达水平下调。XMU-MP-1抑制联合治疗组pYAP、pTAZ的表达，从而促进AXL、CCN1、CCN2的表达。经XMU-MP-1治疗后，wogonin +照射组HCC细胞的增殖能力部分恢复。2 μM XMU-MP-1预处理wogonin +照射组肝癌细胞凋亡逆转。结论枸杞子素可调节hcv - yap /TAZ信号通路，增强hcc的放射敏感性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.