槲皮素通过下调肝癌细胞P4HA2和抑制PI3K/Akt/mTOR轴诱导细胞凋亡的体外研究

IF 1.5 Q4 ONCOLOGY

Cancer reports Pub Date : 2025-05-10 DOI:10.1002/cnr2.70220

Junli Zhang, Jiayi Guo, Ying Qian, Lianchen Yu, Junrao Ma, Biao Gu, Weichun Tang, Yi Li, Hongwei Li, Wenjuan Wu

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引用次数: 0

摘要

槲皮素是一种具有多种活性的天然产物，对恶性肿瘤具有良好的抗肿瘤作用。脯氨酸4-羟化酶II （P4HA2）参与胶原合成对肿瘤细胞的生长至关重要。细胞凋亡是细胞内环境稳定所必需的程序性细胞死亡。然而，槲皮素与细胞凋亡之间的关系，以及P4HA2在这方面的影响，在肝细胞癌（HCC）中尚未明确。目的研究槲皮素对肝癌细胞P4HA2的调控作用及对细胞增殖和凋亡的影响。方法与结果槲皮素能抑制肝癌细胞的生长和增殖，并呈剂量依赖性地诱导细胞凋亡。此外，槲皮素可促进肝癌细胞P4HA2下调，导致细胞凋亡，而敲低P4HA2可增强这一作用。此外，我们用抑制剂（Z-VAD-FMK, LY294002）或激活剂（740Y-P）预处理HCC细胞，发现PI3K/Akt/mTOR通路被槲皮素诱导的细胞凋亡所占据。结论槲皮素通过降低P4HA2和抑制PI3K/Akt/mTOR轴诱导肝癌细胞凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Quercetin Induces Apoptosis Through Downregulating P4HA2 and Inhibiting the PI3K/Akt/mTOR Axis in Hepatocellular Carcinoma Cells: An In Vitro Study

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Quercetin Induces Apoptosis Through Downregulating P4HA2 and Inhibiting the PI3K/Akt/mTOR Axis in Hepatocellular Carcinoma Cells: An In Vitro Study

Background

Quercetin is a natural product with multiple activities, which possesses a promising antitumor effect on malignancies. The involvement of proline 4-hydroxylase II (P4HA2) in collagen synthesis is crucial in the growth of tumor cells. Apoptosis is a programmed cell death requisite for the stability of the intracellular environment. However, the relationship between quercetin and cell apoptosis, as well as the impact of P4HA2 in this connection, has not yet been specified in hepatocellular carcinoma(HCC).

Aims

The present study used HCC cells to investigate how quercetin regulates P4HA2 and influences cell proliferation and apoptosis.

Methods and Results

The outcomes reveal that quercetin can impede the viability and growth of HCC cells and generate cell apoptosis in a dose-dependent manner. Additionally, quercetin prompts downregulation of P4HA2, leading to cell apoptosis in HCC cells, and knocking down P4HA2 can enhance this effect. Furthermore, we pretreated HCC cells with inhibitors (Z-VAD-FMK, LY294002) or activators (740Y-P) and found that the PI3K/Akt/mTOR pathway was occupied with quercetin-induced cell apoptosis.