研究动态
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REG3A通过激活PI3K/Akt信号通路促进卵巢癌细胞的增殖和顺铂耐药。

REG3A promotes proliferation and DDP resistance of ovarian cancer cells by activating the PI3K/Akt signaling pathway.

发表日期:2023 Sep 04
作者: Lingling Jiang, Yinglei Liu, Manhua Liu, Yanli Zheng, Liping Chen, Feng Shan, Jinlong Ji, Yang Cao, Haili Kai, Xinyi Kang
来源: GENES & DEVELOPMENT

摘要:

本研究探讨了再生胰岛源3-α蛋白(REG3A)在卵巢癌(OC)进展中的作用。通过定量实时聚合酶链反应(qRT-PCR)分析了97例OC患者的临床组织中的REG3A表达。通过转染调控OC细胞和顺铂(DDP)耐药OC细胞中的REG3A表达。使用LY294002 (10 μM, PI3K/Akt信号通路抑制剂)处理OC细胞和DDP耐药OC细胞。细胞计数试剂盒-8和甲基噻唑四唑(MTT)法用于细胞增殖和DDP耐药性检测。流式细胞术用于细胞周期和凋亡分析。通过使用裸露小鼠建立异种移植瘤模型研究REG3A对OC细胞体内生长的影响。使用qRT-PCR、Western blot和免疫组化方法研究临床样本、细胞和异种移植瘤组织中的基因表达。结果表明,REG3A在OC患者和细胞中过度表达,与患者预后不良有关。REG3A沉默抑制OC细胞的增殖、DDP耐药性,诱导细胞周期阻滞和凋亡,并降低OC细胞中MDR-1、Cyclin D1、Cleaved caspase 3蛋白和PI3K/Akt信号通路的活性。LY294002处理取消了REG3A对OC细胞增殖、凋亡抑制和DDP耐药性的促进作用。REG3A沉默抑制了OC细胞的体内生长。因此,REG3A通过激活PI3K/Akt信号通路促进OC细胞的增殖和DDP耐药性。REG3A可能是OC的临床治疗的一个有前景的靶点。© 2023 Wiley Periodicals LLC.
This study explored the effect of Regenerating Islet-Derived 3-Alpha (REG3A) on ovarian cancer (OC) progression. REG3A expression was scrutinized in clinical tissues of 97 OC cases by quantitative real-time polymerase chain reaction (qRT-PCR). REG3A expression in OC cells and cisplatin (DDP) resistance OC cells was regulated by transfection. LY294002 (10 μM, inhibitor of the PI3K/Akt signaling pathway) was used to treat OC cells and DDP resistance OC cells. Cell counting kit-8 and methyl-thiazolyl-tetrazolium assays were applied for proliferation and DDP resistance detection. Flow cytometry was utilized for cell cycle and apoptosis analysis. The effect of REG3A on the OC cell in vivo growth was researched by establishing xenograft tumor model via using nude mice using nude mice. The expression of genes in clinical samples, cells and xenograft tumor tissues was investigated by qRT-PCR, Western blot and immunohistochemistry. As a result, REG3A was over-expressed in OC patients and cells, associating with dismal prognosis of patients. REG3A knockdown repressed proliferation, DDP resistance, induced cell cycle arrest and apoptosis of OC cells, and reduced the expression MDR-1, Cyclin D1, Cleaved caspase 3 proteins and the PI3K/Akt signaling pathway activity in OC cells. LY294002 treatment abrogated the promotion effect of REG3A on OC cell proliferation, apoptosis inhibition and DDP resistance. REG3A knockdown suppressed the in vivo growth of OC cells. Thus, REG3A promoted proliferation and DDP resistance of OC cells by activating the PI3K/Akt signaling pathway. REG3A might be a promising target for the clinical treatment of OC.© 2023 Wiley Periodicals LLC.