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β-arrestin-2 up-regulates toll-like receptor 2 signaling and inhibits apoptosis in human endometrial cancer heterotransplants in nude mice

Authors
  • Hong, Fanling1
  • Zhang, Yujun2
  • Cheng, Wenjin1
  • Sun, Xiuli1
  • Wang, Jianliu1
  • 1 Peking University People’s Hospital, Department of Obstetrics and Gynecology, No.11 Xizhimen South Street, Xicheng Dist, Beijing, 100044, China , Beijing (China)
  • 2 Peking University People’s Hospital, The Clinical Institute of Molecular Biology & Central Lab, No.11 Xizhimen South Street, Xicheng Dist, Beijing, 100044, China , Beijing (China)
Type
Published Article
Journal
BMC Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Nov 01, 2019
Volume
19
Issue
1
Identifiers
DOI: 10.1186/s12885-019-6254-4
Source
Springer Nature
Keywords
License
Green

Abstract

Backgroundβ-arrestin-2(Arr2) functions as an anti-apoptotic factor and affects cell proliferation, but its downstream molecular pathway in endometrial carcinoma (EC) is still unclear. This study aimed to investigate the effects of the stable overexpression of Arr2 on the proliferation and apoptosis of human EC heterotransplants and the expression of associated molecules, including Toll-like receptor 2(TLR2), serine-threonine kinase Akt (Akt), glycogen synthase kinase-3β(GSK3β) and some typical inflammatory cytokines such as NF-κB p56, TNF-α and IL-6 & IL-8.MethodsHuman EC cell line Ishikawa, stably transfected with Arr2 full-length plasmid, was injected subcutaneously into nude mice. They were treated with 0, 10, 20 mg/kg paclitaxel and the volume and weight of the tumor tissue were measured and calculated. The necrotic index were assessed by H&E staining and microscopic observation. The levels of caspase-3, caspase-9, TLR2, NF-κB p56, Akt, GSK3β were measured by western blot, and the levels of TNF-α, IL-6, IL-8 were measured by real-time PCR.ResultsWe found that Arr2 overexpression promoted the growth of human EC heterotransplants. Arr2 attenuated the promotion of caspase-3 and caspase-9 by paclitaxel and mediated the increase of TLR2 and several inflammatory cytokines. The levels of Akt and GSK3β were not affected.ConclusionArr2 overexpression was associated with the increase of TLR2 and several inflammatory factors, meanwhile inhibited paclitaxel-induced anti-tumor effect on human EC heterotransplants.

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