Hepatocellular carcinoma (HCC), which is the third leading cause of cancer-related mortality in the world, presents a significant medical challenge. Triptolide (TP) has been identified as an effective therapeutic drug for HCC. However, its precise therapeutic mechanism is still unknown. Understanding the mechanism of action of TP against HCC is crucial for its implementation in the field of HCC treatment. We hypothesize that the anti-HCC actions of TP might be related to its modulation of HCC lipid metabolism given the crucial role that lipid metabolism plays in promoting the progression of HCC. In this work, we first demonstrate that, both in vitro and in vivo, TP significantly reduces lipid accumulation in HCC cells. Additionally, we notice that lipoprotein lipase (LPL) expression is markedly upregulated in HCC, and that its levels are positively connected with the disease’s progression. It is interesting to note that TP dramatically reduces LPL activity, which in turn prevents HCC growth and reduces lipid accumulation. Additionally, the effect of TP on LPL is a direct correlation. These results definitely demonstrate that TP protects hepatocytes against abnormal accumulation of lipids by transcriptionally suppressing LPL, which reduces the development of HCC. This newly identified pathway provides insight into the process through which TP exerts its anti-HCC actions.
肝细胞癌（HCC）是全球癌症相关死亡的第三大原因，构成重大医学挑战。雷公藤甲素（TP）已被证实是治疗HCC的有效药物，但其确切治疗机制尚不明确。阐明TP抗HCC的作用机制对其在HCC治疗领域的应用至关重要。鉴于脂质代谢在促进HCC进展中的关键作用，我们推测TP的抗HCC作用可能与其调节HCC脂质代谢相关。本研究首次通过体内外实验证明，TP能显著降低HCC细胞的脂质蓄积。同时我们发现脂蛋白脂肪酶（LPL）在HCC中表达显著上调，且其水平与疾病进展呈正相关。值得注意的是，TP能显著抑制LPL活性，从而阻断HCC生长并减少脂质堆积。此外，TP对LPL的调控呈直接相关性。这些结果明确证实，TP通过转录抑制LPL保护肝细胞免受异常脂质蓄积，从而抑制HCC发展。这一新发现的作用通路为阐释TP抗HCC的作用机制提供了重要见解。
肿瘤(癌症)患者之家