β-arrestin-2 up-regulates toll-like receptor 2 signaling and inhibits apoptosis in human endometrial cancer heterotransplants in nude mice
Autor: | Xiuli Sun, Jianliu Wang, Yujun Zhang, Fanling Hong, Wenjin Cheng |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Cancer Research
Mice Nude Apoptosis Endometrial carcinoma lcsh:RC254-282 Proinflammatory cytokine Mice Western blot Invasion Cell Line Tumor Genetics medicine Animals Humans Receptor Protein kinase B Cell proliferation Glycogen Synthase Kinase 3 beta medicine.diagnostic_test Chemistry Cell growth Kinase β-arrestin-2 NF-kappa B lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens beta-Arrestin 2 Endometrial Neoplasms Gene Expression Regulation Neoplastic Oncogene Protein v-akt TLR2 Toll-like receptor 2 Oncology Uterine Neoplasms Cancer research Cytokines Heterografts Female Inflammation Mediators Neoplasm Transplantation Research Article Signal Transduction |
Zdroj: | BMC Cancer, Vol 19, Iss 1, Pp 1-9 (2019) BMC Cancer |
ISSN: | 1471-2407 |
Popis: | Background β-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. Methods Human 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. Results We 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. Conclusion Arr2 overexpression was associated with the increase of TLR2 and several inflammatory factors, meanwhile inhibited paclitaxel-induced anti-tumor effect on human EC heterotransplants. |
Databáze: | OpenAIRE |
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