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抵抗素在上皮性卵巢癌中的表达促进卵巢癌细胞的增殖和迁移,从而恶化预后。

Resistin Expression in Epithelial Ovarian Cancer promotes the Proliferation and Migration of Ovarian Cancer Cells to Worsen Prognosis.

作者信息

Pang Li, Chang Xiaohan

机构信息

Department of Obstetrics and Gynecology, ShengJing Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

J Cancer. 2021 Sep 23;12(22):6796-6804. doi: 10.7150/jca.62496. eCollection 2021.

Abstract

Epithelial ovarian cancer (EOC) is the most common gynecological cancer in women. Resistin, an inflammatory adipocytokine, is associated with obesity, insulin resistance, and various cancer types We investigated resistin expression in tissues and its association with the clinicopathological characteristics and prognosis of patients with EOC. The SKOV3 and CAOV3 cell lines were treated with exogenous resistin and rapamycin (resistin inhibitor), and the expression of mTOR in SKOV3 and CAOV3 cells was measured. Cell proliferation was measured using the CCK-8 assay. Western blotting analysis was performed to examine the phosphorylation of P70S6K and mTOR. Wound healing and Transwell analyses were conducted to examine the effect of resistin on the migration of SKOV3 and CAOV3 cells. High resistin expression was positively correlated with the pathological grade ( = 0.017) and lymph node metastasis ( = 0.045). However, resistin expression was not correlated with age, FIGO stage, or residual tumor after initial laparotomy ( > 0.05). Cox multivariate analysis showed that resistin expression was an independent factor for determining disease-free survival, whereas lymph node metastasis, resistin expression, and age (≥55 years) were independent factors affecting overall survival. Exogenous resistin induced ovarian cancer cell proliferation, whereas rapamycin had the opposite effect. Resistin promoted the proliferation of ovarian cancer cells via the mTOR signaling pathway and was associated with phosphorylating P70S6K. Furthermore, resistin promoted the migration of ovarian cancer cells. Resistin may promote the occurrence of ovarian cancer and is related to the prognosis of patients. This protein may also affect the proliferation of EOC cells through the mTOR signaling pathway. Therefore, resistin shows potential as a molecular therapeutic target in ovarian cancer.

摘要

上皮性卵巢癌(EOC)是女性中最常见的妇科癌症。抵抗素是一种炎症性脂肪细胞因子,与肥胖、胰岛素抵抗和多种癌症类型相关。我们研究了抵抗素在组织中的表达及其与EOC患者临床病理特征和预后的关系。用外源性抵抗素和雷帕霉素(抵抗素抑制剂)处理SKOV3和CAOV3细胞系,并检测SKOV3和CAOV3细胞中mTOR的表达。使用CCK-8法检测细胞增殖。进行蛋白质印迹分析以检测P70S6K和mTOR的磷酸化。进行伤口愈合和Transwell分析以检测抵抗素对SKOV3和CAOV3细胞迁移的影响。抵抗素高表达与病理分级(P = 0.017)和淋巴结转移(P = 0.045)呈正相关。然而,抵抗素表达与年龄、国际妇产科联盟(FIGO)分期或初次剖腹手术后的残留肿瘤无关(P>0.05)。Cox多因素分析表明,抵抗素表达是决定无病生存的独立因素,而淋巴结转移、抵抗素表达和年龄(≥55岁)是影响总生存的独立因素。外源性抵抗素诱导卵巢癌细胞增殖,而雷帕霉素则有相反的作用。抵抗素通过mTOR信号通路促进卵巢癌细胞增殖,并与P70S6K磷酸化有关。此外,抵抗素促进卵巢癌细胞的迁移。抵抗素可能促进卵巢癌的发生,并与患者的预后相关。这种蛋白质也可能通过mTOR信号通路影响EOC细胞的增殖。因此,抵抗素在卵巢癌中显示出作为分子治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c7/8518001/ae8a3a594ce2/jcav12p6796g001.jpg

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