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首页> 外文期刊>Biology Open >Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway
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Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway

机译:抑制HE4的表达通过抑制JAK / STAT3途径来抑制卵巢癌的侵袭性细胞生长和恶性进展

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Human epididymis protein 4 (HE4) is well known to be a predictor of ovarian cancer clinically. HE4 is reported to play crucial roles in ovarian cancer progression and metastasis. The purpose of the present study was to explore its biological role and molecular mechanism in ovarian cancer. In our study, we found that expression levels of HE4 in tissues, serum and urine in ovarian cancer were upregulated compared to healthy and benign groups. HE4 expression was elevated in ovarian cancer cells. Knockdown of HE4 dampened cell proliferation and Ki67 expression, as well as enhanced apoptosis, caspase-3 activity and cleaved-caspase-3 expression. In addition, HE4 downregulation repressed invasion and migration capabilities of ovarian cancer cells. Western blot analyses showed that knockdown of HE4 reduced the levels of matrix metalloproteinases (MMP-2 and MMP-9) and inhibited epithelial to mesenchymal transition (EMT) in ovarian cancer cells.In vivoanimal experiments revealed that HE4 downregulation constrained the growth of xenograft tumor. Mechanism research showed that knockdown HE4 inhibited the activity of JAK/STAT3 pathwayin vitroandin vivo. In conclusion, our findings reported that knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway, which provides valuable insights to contribute to develop novel HE4-targeted therapies.
机译:人附睾蛋白4(HE4)是临床上卵巢癌的预测因子。据报道,HE4在卵巢癌的进展和转移中起关键作用。本研究的目的是探讨其在卵巢癌中的生物学作用和分子机制。在我们的研究中,我们发现与健康和良性组相比,卵巢癌组织,血清和尿液中HE4的表达水平上调。 HE4表达在卵巢癌细胞中升高。击倒HE4会抑制细胞增殖和Ki67表达,并增强细胞凋亡,caspase-3活性和caspase-3裂解表达。此外,HE4下调抑制了卵巢癌细胞的侵袭和迁移能力。蛋白质印迹分析表明,敲除HE4可以降低卵巢癌细胞中基质金属蛋白酶(MMP-2和MMP-9)的水平,并抑制上皮向间质转化(EMT)。 。机制研究表明,敲低的HE4在体内外均抑制JAK / STAT3途径的活性。总之,我们的发现报告说,敲低HE4可以通过抑制JAK / STAT3途径来抑制卵巢癌的侵袭性细胞生长和恶性进展,这为开发新的针对HE4的疗法提供了宝贵的见识。

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