分泌型卷曲相关蛋白1通过抑制Wnt/β-连环蛋白信号通路来抑制上皮性卵巢癌。
SFRP1 inhibited the epithelial ovarian cancer through inhibiting Wnt/β-catenin signaling.
作者信息
Zhang Hao, Sun Duohe, Qiu Jianping, Yao Liangqing
机构信息
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, P.R. China.
Department of Obstetrics and Gynecology, Shanghai Jiaotong University, Affiliated Sixth People's Hospital South Campus, Shanghai, 201499, P.R. China.
出版信息
Acta Biochim Pol. 2019 Nov 26;66(4):393-400. doi: 10.18388/abp.2019_2757.
BACKGROUND
Epithelial ovarian cancer is the most malignant gynecologic neoplasm accounting for 90% of the ovarian cancer patients.
OBJECTIVE
Researchers proved that epigenetic alterations could disrupt gene expression as often as genetic alterations. Secreted frizzed related protein (SFRP1), a Wnt antagonist, exerts a significant effect on ovarian cancer. The aim of this research was to investigate the effects and the mechanism of action of SFRP1 on epithelial ovarian cancer.
METHODS
Clinical specimens (including fallopian tubes epithelium from 60 epithelial ovarian cancer patients' and 20 healthy subjects who were undergoing surgical treatments), transgenic mice (overexpressing SFRP1 gene), and 4 epithelial ovarian cancer cell lines (including OVCAR4, SKOV3, COV644, TOV21G) were used in this study. Overexpression of SFRP1 in cells was carried out on OVCAR4 cells by transfection using Lipofectamine 2000. Gene transcription was analyzed by qRT-PCR. The methylation of SFRP1 gene was quantified by methylation-specific PCR. The level of protein expression was measured by Western blot or immunohistochemistry analysis. Cell proliferation was analyzed by CCK8 methods. The ability of cell migration and invasion were measured by wound healing assay and transwell assay.
RESULTS
Abnormal expression level and hypermethylation status of SFRP1 were found in clinical epithelial ovarian cancer samples and cell lines. We observed that SFRP1 knockdown could promote proliferation, migration and invasion abilities of epithelial ovarian cancer cells. Additionally, we discovered a potential inhibitory effect of SFRP1 on Wnt/β-catenin signaling pathway in epithelial ovarian cancer cells. Furthermore, the anti-tumor effect of SFRP1 was tested in SFRP1 transgenic mice.
CONCLUSION
SFRP1 inhibited epithelial ovarian cancer through inhibiting Wnt/β-catenin pathway, suggesting that SFRP1 could be considered as a potential therapeutic target in epithelial ovarian cancer.
背景
上皮性卵巢癌是最恶性的妇科肿瘤，占卵巢癌患者的90%。
目的
研究人员证明，表观遗传改变与基因改变一样，经常会破坏基因表达。分泌型卷曲相关蛋白1（SFRP1）是一种Wnt拮抗剂，对卵巢癌有显著影响。本研究的目的是探讨SFRP1对上皮性卵巢癌的作用及其作用机制。
方法
本研究使用了临床标本（包括60例上皮性卵巢癌患者和20例接受手术治疗的健康受试者的输卵管上皮）、转基因小鼠（过表达SFRP1基因）和4种上皮性卵巢癌细胞系（包括OVCAR4、SKOV3、COV644、TOV21G）。通过使用Lipofectamine 2000转染，在OVCAR4细胞上实现SFRP1在细胞中的过表达。通过qRT-PCR分析基因转录。通过甲基化特异性PCR定量SFRP1基因的甲基化。通过蛋白质印迹或免疫组织化学分析测量蛋白质表达水平。通过CCK8法分析细胞增殖。通过伤口愈合试验和transwell试验测量细胞迁移和侵袭能力。
结果
在临床上皮性卵巢癌样本和细胞系中发现SFRP1表达水平异常和高甲基化状态。我们观察到SFRP1基因敲低可促进上皮性卵巢癌细胞的增殖、迁移和侵袭能力。此外，我们发现SFRP1对上皮性卵巢癌细胞中的Wnt/β-连环蛋白信号通路具有潜在的抑制作用。此外，在SFRP1转基因小鼠中测试了SFRP1的抗肿瘤作用。
结论
SFRP1通过抑制Wnt/β-连环蛋白通路抑制上皮性卵巢癌，提示SFRP1可被视为上皮性卵巢癌的潜在治疗靶点。
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