STEAP4 inhibits cisplatin-induced chemotherapy resistance through suppressing PI3K/AKT in hepatocellular carcinoma.
STEAP4 inhibits cisplatin-induced chemotherapy resistance through suppressing PI3K/AKT in hepatocellular carcinoma.
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DOI：
10.1186/s40170-023-00323-1
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发表时间：
2023-12-18
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
化疗耐药是导致肝细胞癌（HCC）死亡的主要原因。探索耐药发生机制是肝癌治疗的迫切需要。在这里，我们发现STEAP 4在复发的HCC患者中显著下调。STEAP 4水平低的患者预后差，提示STEAP 4可能抑制化疗耐药。细胞活力测定、集落形成测定、凋亡测定、软琼脂生长测定和肿瘤动物模型显示STEAP 4抑制顺铂耐药性。机制分析表明STEAP 4通过直接与AKT相互作用抑制PI 3 K/AKT通路。STEP 4和AKT的双敲低显著抑制顺铂耐药性。我们还发现STEAP 4表达与临床标本中PI 3 K/AKT通路活性呈负相关。综上所述，我们的研究结果表明STEAP 4通过抑制PI 3 K/AKT通路活性来抑制顺铂耐药，为HCC治疗提供了靶点。
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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影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A
影响因子：
8
作者：
Korkmaz, CG;Korkmaz, KS;Saatcioglu, F
通讯作者：
Saatcioglu, F
影响因子：
5
作者：
Catalan, Victoria;Gomez-Ambrosi, Javier;Fruehbeck, Gema
通讯作者：
Fruehbeck, Gema
影响因子：
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作者：
Wu L;Mao C;Ming X
通讯作者：
Ming X
影响因子：
0.4
作者：
Liu, Y. R.;Xu, H. M.
通讯作者：
Xu, H. M.