RESUMO
Ovarian cancer is the leading cause of cancer associated mortality in the female reproductive system. Interleukin (IL)33 and its receptor IL 1 receptor like 1 (also termed ST2) are expressed by many cell types including epithelial cells. The role of IL33 in the pathogenesis of neoplasia remains controversial. The authors previously demonstrated that IL33 inhibits the growth of pancreatic cancer cells. The present study was performed to explore if IL33 has any direct effects on ovarian cancer cells. A clonogenic survival assay, immunohistochemistry (IHC), proliferation kit and caspase3 activity kit were all used to evaluate the direct effects of IL33 on cell proliferation and apoptosis of a widely studied ovarian cancer cell line, A2780. The possible molecular mechanisms were further evaluated with reverse transcriptionpolymerase chain reaction and IHC. It was demonstrated that the percentage of colonies and the optical density value of cancer cells were all increased in the presence of IL33; however, the relative caspase3 activity in cancer cells was decreased in the presence of IL33. Molecular mechanism studies revealed that the proproliferative effect of IL33 on cancer cells was associated with decreased levels of p27, and the antiapoptotic effect of IL33 was associated with levels of Fas cell surface death receptor (Fas) and tumor necrosis factorrelated apoptosisinducing ligand receptor 1 (TRAILR1). Therefore, IL33 promoted proliferation and inhibited apoptosis of ovarian cancer cells by downregulation of p27, Fas and TRAILR1. Contrary to previous studies demonstrating an antitumor effort in pancreatic cancer, the results of the present study indicated that IL33 exhibited a significant oncopromoting effect on ovarian cancer. Accordingly, the inhibition of IL33 may be a promising therapeutic strategy for ovarian cancer.
Assuntos
Interleucina-33/metabolismo , Neoplasias Ovarianas/patologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação para Baixo , Feminino , Humanos , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptor fas/metabolismoRESUMO
Interleukin-21 (IL-21), produced predominantly by CD4+ T cells and natural killer T (NKT) cells, is a newly discovered member of the common γ-chain family of cytokines. It has been implicated in many immunological processes and has been linked to autoimmune diseases, allergies and other inflammatory diseases. In recent years, the role for IL-21 in the pathogenesis of cancer has also been extensively studied. In this review, we will discuss recent advances concerning the role of IL-21 in immunological processes and the pathogenesis of cancer.