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

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.

Protective effects of miR‑155‑5p silencing on IFN‑γ‑induced apoptosis and inflammation in salivary gland epithelial cells

“…Li et al (55) demonstrated that the overexpression of ARRB2 may inhibit the release of proinflammatory cytokines and decrease experimental arthritis severity. In addition, ARRB2 has exhibited antiapoptotic effects in human endometrial cancer heterotransplants in nude mice (56,57). The results of the present study demonstrated that overexpression of ARRB2 reversed the effects of miR-155-5p overexpression on the inflammatory response, apoptosis and the NF-κB signaling pathway in this inflammatory lesion model.…”

A Novel Transcription Factor-Based Prognostic Signature in Endometrial Cancer: Establishment and Validation

“…RT-PCR and Western blot were conducted according to a previously described method. 22 , 23 The cell proliferation activity was tested by a Cell Counting Kit CCK-8 (Dojindo, Japan) assay at 450 nm in a microplate reader.…”

Deciphering the signaling mechanisms of β‐arrestin1 and β‐arrestin2 in regulation of cancer cell cycle and metastasis

“…As already mentioned in several instances in the article, the β‐arr family is the most popular activator for signaling tumorigenic pathways (Cianfrocca et al, 2014, 2017). Several studies have reported that aberrant β‐arr2 protein expression is associated with different types of human malignancies (Figure 4) (Hong et al, 2019; Sun et al, 2016). For instance, in breast cancer cell lines, β‐arr2 is highly expressed in the highly metastatic cells and tumors, promoting cancer cell migration and invasion (Czogalla et al, 2020).…”

“…β‐Arrestin 2 mediated activation of Akt signal leads to the formation of GPR35/β‐arrestin‐2/Akt loop, promoting chemoresistance in NSCLC (W. Wang et al, 2018). To promote a tumorigenic environment, a recent study implied that β‐arr2 is positively associated with the increase of TLR2, which leads to the release of inflammatory cytokines (Hong et al, 2019).…”