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下调 PTPN18 可以抑制子宫内膜癌细胞的增殖和转移,促进其凋亡。

Downregulation of PTPN18 can inhibit proliferation and metastasis and promote apoptosis of endometrial cancer.

机构信息

Key Laboratory of Cell and Molecular Genetic Translational Medicine in Hainan Province, Hainan General Hospital, Haikou, Hainan, China.

Department of Gynaecology and Obstetrics, Hainan General Hospital, Haikou, Hainan, China.

出版信息

Clin Exp Pharmacol Physiol. 2019 Aug;46(8):734-742. doi: 10.1111/1440-1681.13098. Epub 2019 May 30.

DOI:10.1111/1440-1681.13098
PMID:31034093
Abstract

Endometrial cancer is one of the chief culprits threatening women's lives. Although numerous epidemiological experiments have been carried out into the aetiology of endometrial cancer, the cause of the disease has been unclear up to now. In recent years, PTPN18, a member of the protein tyrosine phosphatases (PTP) family predicted to be tumour suppressors or oncogenes, has been confirmed to participate in the occurrence and progression of many cancers. Few studies, however, have explained the role in the endometrial cancer. So, it caught our attention to explore if PTPN18 participates in and plays a regulatory role in the proliferation, apoptosis, and metastasis of endometrial cancer. In our results, we found that PTPN18 was overexpressed in endometrial cancer tissue compared to paracancerous tissue by immunohistochemistry. Not only that, silencing of PTPN18 in endometrial cancer cell lines (HEC-1-A and HEC-1-B) can significantly impair proliferation detected by CCK8 assay and flow cytometry (FCM) analyses and inhibit the metastasis of endometrial cancer cells shown by the scratch test and the Transwell experiment. PTPN18 knockdown can promote the apoptosis of endometrial cancer. In addition, nude mice tumour formation assay confirmed the results in vivo. Although the exact function of PTPN18 in endometrial cancer is unclear, the targeted therapy drugs enhancing PTPN18 may be considered in the future treatment of endometrial carcinoma.

摘要

子宫内膜癌是威胁女性生命的主要元凶之一。尽管已经进行了大量的流行病学实验来研究子宫内膜癌的病因,但到目前为止,这种疾病的病因还不清楚。近年来,PTPN18 作为一种蛋白质酪氨酸磷酸酶(PTP)家族成员,被预测为抑癌基因或癌基因,已被证实参与了许多癌症的发生和发展。然而,很少有研究解释其在子宫内膜癌中的作用。因此,我们注意到探讨 PTPN18 是否参与并在子宫内膜癌的增殖、凋亡和转移中发挥调节作用。在我们的研究结果中,我们通过免疫组织化学发现 PTPN18 在子宫内膜癌组织中的表达高于癌旁组织。不仅如此,通过 CCK8 检测和流式细胞术(FCM)分析,沉默子宫内膜癌细胞系(HEC-1-A 和 HEC-1-B)中的 PTPN18 可以显著抑制增殖,并通过划痕实验和 Transwell 实验抑制子宫内膜癌细胞的转移。PTPN18 敲低可以促进子宫内膜癌的凋亡。此外,裸鼠肿瘤形成实验在体内证实了这些结果。尽管 PTPN18 在子宫内膜癌中的确切功能尚不清楚,但未来可能会考虑使用增强 PTPN18 的靶向治疗药物来治疗子宫内膜癌。

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