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<p>Hepatocellular carcinoma (HCC) is characterized by a subtle onset, rapid development, and high malignancy. Traditional treatments have struggled to cure patients with advanced HCC. Crebanine is an isoquinoline aporphine alkaloid extracted from <i>Stephania venosa</i>. Few studies have focused on the therapeutic potential and molecular mechanisms of crebanine in HCC. Herein, to comprehensively evaluate the anti-HCC effect of crebanine in HCC&#xa0;and to further investigate the underlying mechanisms, potential therapeutic role of crebanine against HCC malignancy was assessed through <i>in vitro</i> and <i>in vivo</i> experiments. We carried out a panel of experiments covering cell viability, colony formation, apoptosis detection, migration, invasion and western blot analysis. Results revealed that crebanine suppresses proliferation, migration and invasion, and triggers apoptosis in HepG2 and Huh7 cells. Mechanistically, crebanine treatment increased DUSP1 expression while decreasing EZH2 and p-Akt expressions. Crebanine promoted DUSP1&#xa0;transcription through repressing EZH2 expression, thereby inhibiting Akt phosphorylation. Knockdown of DUSP1 diminished the anti-HCC effects of crebanine while activating Akt signaling. Overexpression of EZH2 abolished crebanine-induced DUSP1 upregulation and the cytostatic effects in HCC both <i>in vitro</i> and vivo. Overall, crebanine effectively suppresses HCC tumor growth and progression via modulation of the EZH2/DUSP1/Akt signaling pathway. Crebanine shows potential as a promising therapeutic agent for HCC treatment.</p> Graphical Abstract <p>1. Crebanine exerts potent inhibitory effects on HCC both <i>in vitro</i> and <i>in vivo</i>.</p> <p>2. Crebanine abrogates EZH2-induced transcriptional silencing of DUSP1, consequently hindering AKT signaling activation.</p> <p>3. Crebanine impedes the malignant progression of HCC by modulating the EZH2/DUSP1/AKT signaling cascade.</p> <p></p>

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EZH2/DUSP1/Akt signaling axis mediates the inhibitory effect of crebanine on hepatocellular carcinoma progression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Jinxia Qi,
  • Zhikai Wen,
  • Yanju Ren,
  • Gang Huang,
  • Yuan Wang,
  • Qingqing Ruan,
  • Chunmei Wen,
  • Jiale Xu,
  • Mengyao Wang,
  • Xingyue Wang,
  • Hanbin Chen,
  • Yihu Zheng,
  • Jie Deng

摘要

Hepatocellular carcinoma (HCC) is characterized by a subtle onset, rapid development, and high malignancy. Traditional treatments have struggled to cure patients with advanced HCC. Crebanine is an isoquinoline aporphine alkaloid extracted from Stephania venosa. Few studies have focused on the therapeutic potential and molecular mechanisms of crebanine in HCC. Herein, to comprehensively evaluate the anti-HCC effect of crebanine in HCC and to further investigate the underlying mechanisms, potential therapeutic role of crebanine against HCC malignancy was assessed through in vitro and in vivo experiments. We carried out a panel of experiments covering cell viability, colony formation, apoptosis detection, migration, invasion and western blot analysis. Results revealed that crebanine suppresses proliferation, migration and invasion, and triggers apoptosis in HepG2 and Huh7 cells. Mechanistically, crebanine treatment increased DUSP1 expression while decreasing EZH2 and p-Akt expressions. Crebanine promoted DUSP1 transcription through repressing EZH2 expression, thereby inhibiting Akt phosphorylation. Knockdown of DUSP1 diminished the anti-HCC effects of crebanine while activating Akt signaling. Overexpression of EZH2 abolished crebanine-induced DUSP1 upregulation and the cytostatic effects in HCC both in vitro and vivo. Overall, crebanine effectively suppresses HCC tumor growth and progression via modulation of the EZH2/DUSP1/Akt signaling pathway. Crebanine shows potential as a promising therapeutic agent for HCC treatment.

Graphical Abstract

1. Crebanine exerts potent inhibitory effects on HCC both in vitro and in vivo.

2. Crebanine abrogates EZH2-induced transcriptional silencing of DUSP1, consequently hindering AKT signaling activation.

3. Crebanine impedes the malignant progression of HCC by modulating the EZH2/DUSP1/AKT signaling cascade.