STEAP4 通过抑制肝细胞癌中的 PI3K/AKT 抑制顺铂诱导的化疗耐药性

IF 6 3区医学 Q1 CELL BIOLOGY

Cancer & Metabolism Pub Date : 2023-12-18 DOI:10.1186/s40170-023-00323-1

Binhui Xie, Baiyin Zhong, Zhenxian Zhao, Jie Hu, Jianqiong Yang, Yuankang Xie, Jianhong Zhang, Jianting Long, Xuewei Yang, Heping Li

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引用次数: 0

摘要

化疗耐药性是导致肝细胞癌（HCC）死亡的主要原因。探索耐药性的产生机制是 HCC 治疗的迫切需要。在这里，我们发现 STEAP4 在复发的 HCC 患者中明显下调。低STEAP4的患者预后较差，这表明STEAP4可能抑制化疗耐药。细胞活力测定、集落形成测定、细胞凋亡测定、软琼脂生长测定和肿瘤动物模型显示，STEAP4可抑制顺铂耐药性。机理分析表明，STEAP4 通过直接与 AKT 相互作用来抑制 PI3K/AKT 通路。STEP4 和 AKT 的双重敲除可明显抑制顺铂耐药。我们还发现，在临床标本中，STEAP4的表达与PI3K/AKT通路的活性呈负相关。总之，我们的研究结果表明 STEAP4 通过抑制 PI3K/AKT 通路的活性来抑制顺铂耐药，为 HCC 治疗提供了靶点。

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STEAP4 inhibits cisplatin-induced chemotherapy resistance through suppressing PI3K/AKT in hepatocellular carcinoma

Chemotherapy resistance is the leading cause for hepatocellular carcinoma (HCC)-induced death. Exploring resistance generation mechanism is an urgent need for HCC therapy. Here, we found STEAP4 was significantly downregulated in HCC patients with recurrence. Patients with low STEAP4 had poor outcome, suggesting STEAP4 might inhibit chemotherapy resistance. Cell viability assay, colony formation assay, apoptosis assay, soft agar growth assay, and tumor animal model showed STEAP4 inhibited cisplatin resistance. Mechanism analysis showed STEAP4 inhibited PI3K/AKT pathway through directly interacting with AKT. Double knockdown of STEP4 and AKT significantly inhibited cisplatin resistance. We also found STEAP4 expression was negatively correlated with PI3K/AKT pathway activity in clinic specimens. In summary, our findings suggested STEAP4 inhibited cisplatin resistance through suppressing PI3K/AKT pathway activity, providing a target for HCC therapy.

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来源期刊

Cancer & Metabolism Multiple-

自引率

1.70%

发文量

审稿时长

14 weeks

期刊介绍： Cancer & Metabolism welcomes studies on all aspects of the relationship between cancer and metabolism, including: -Molecular biology and genetics of cancer metabolism -Whole-body metabolism, including diabetes and obesity, in relation to cancer -Metabolomics in relation to cancer; -Metabolism-based imaging -Preclinical and clinical studies of metabolism-related cancer therapies.