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人绒毛膜促性腺激素参与调节卵巢癌细胞中的血管生成拟态和缺氧诱导因子-1α表达。

Involvement of human chorionic gonadotropin in regulating vasculogenic mimicry and hypoxia-inducible factor-1α expression in ovarian cancer cells.

作者信息

Su Min, Xu Xiangxiang, Wei Weiwei, Gao Sainan, Wang Xiaoying, Chen Caoyi, Zhang Yuquan

机构信息

Department of Obstetrics and Gynecology, The Affiliated Hospital of Nantong University, No 20, Xisi Rd, Nantong, 226001 People's Republic of China.

Suzhou Municipal Hospital, Suzhou, China.

出版信息

Cancer Cell Int. 2016 Jun 24;16:50. doi: 10.1186/s12935-016-0327-0. eCollection 2016.

DOI:10.1186/s12935-016-0327-0
PMID:27346985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4919850/
Abstract

BACKGROUND

Human chorionic gonadotropin (hCG) can play a crucial role in angiogenesis. In the present study, we focused on hCG to gain insight into its potential effects on vasculogenic mimicry (VM) in ovarian cancer cells.

METHODS

Ovarian cancer OVCAR-3 cells were incubated with different concentrations of recombinant hCG in 3-dimensional cultures. VM was identified by morphological observations and vascular endothelial cell marker detection in OVCAR-3 cells. Expression of hCG, hypoxia-inducible factor-1α (HIF-1α), and the endothelial cell markers CD31, VEGF, and factor VIII were detected by reverse transcription polymerase chain reaction and western blotting. The effect of hCG on endothelial cell-marker expression in ovarian cancer cells was further explored using small interfering RNA (siRNA) and plasmid-based approaches.

RESULTS

Incubation of OVCAR-3 cells with recombinant hCG induced vessel-like network formation, which was accompanied by significant elevation of vascular marker expression. Attenuation of hCG expression by siRNA in OVCAR-3 cells suppressed the expression of endothelial cell markers and HIF-1α by tumour cells. Overexpression of hCG in OVCAR-3 cells resulted in increased expression of endothelial cell markers and HIF-1α.

CONCLUSIONS

HCG was crucial for changing the phenotype of OVCAR-3 cells to endothelial-like cells. The effect of hCG induction on VM in ovarian cancer cells is potentially associated with HIF-1α.

摘要

背景

人绒毛膜促性腺激素(hCG)在血管生成中可发挥关键作用。在本研究中,我们聚焦于hCG,以深入了解其对卵巢癌细胞中血管生成拟态(VM)的潜在影响。

方法

将卵巢癌OVCAR - 3细胞在三维培养中与不同浓度的重组hCG孵育。通过形态学观察和OVCAR - 3细胞中血管内皮细胞标志物检测来鉴定VM。采用逆转录聚合酶链反应和蛋白质免疫印迹法检测hCG、缺氧诱导因子-1α(HIF - 1α)以及内皮细胞标志物CD31、VEGF和因子VIII的表达。使用小干扰RNA(siRNA)和基于质粒的方法进一步探究hCG对卵巢癌细胞中内皮细胞标志物表达的影响。

结果

用重组hCG孵育OVCAR - 3细胞可诱导形成血管样网络,同时血管标志物表达显著升高。在OVCAR - 3细胞中通过siRNA减弱hCG表达可抑制肿瘤细胞中内皮细胞标志物和HIF - 1α的表达。在OVCAR - 3细胞中过表达hCG导致内皮细胞标志物和HIF - 1α表达增加。

结论

hCG对于将OVCAR - 3细胞的表型转变为内皮样细胞至关重要。hCG诱导对卵巢癌细胞中VM的影响可能与HIF - 1α有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/4919850/21cca4325b75/12935_2016_327_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/4919850/94d644f31143/12935_2016_327_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/4919850/1ff98eb81295/12935_2016_327_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/4919850/3958cb3cdce3/12935_2016_327_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/4919850/21cca4325b75/12935_2016_327_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/4919850/94d644f31143/12935_2016_327_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/4919850/1ff98eb81295/12935_2016_327_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/4919850/3958cb3cdce3/12935_2016_327_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2eb/4919850/21cca4325b75/12935_2016_327_Fig4_HTML.jpg

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