RESUMO
BACKGROUND: Previous studies have shown that COX-2 inhibitors inhibit cancer cell proliferation. However, the molecular mechanism remains elusive. METHODS: Prostate cancer LNCaP, 22Rv1, and PC3 cells were cultured and treated with the COX-2 inhibitors celecoxib and CAY10404. Knockdown of COX-2 in LNCaP cells was carried out using lentiviral vector-loaded COX-2 shRNA. Cell cycle progression and cell proliferation were analyzed by flow cytometry, microscopy, cell counting, and the MTT assay. The antagonists of EP1, EP2, EP3, and EP4 were used to examine the effects of the PGE2 signaling. The effect of COX-2 inhibitors and COX-2 knockdown on expression of the kinetochore/centromere genes and proteins was determined by RT-PCR and immunoblotting. RESULTS: Treatment with the COX-2 inhibitors celecoxib and CAY10404 or knockdown of COX-2 significantly inhibited prostate cancer cell proliferation. Flow-cytometric analysis and immunofluorescent staining confirmed the cell cycle arrested at the G2/M phase. Biochemical analysis showed that inhibition of COX-2 or suppression of COX-2 expression induced a dramatic down-regulation of key proteins in the kinetochore/centromere assembly, such as ZWINT, Cdc20, Ndc80, CENP-A, Bub1, and Plk1. Furthermore, the EP1 receptor antagonist SC51322, but not the EP2, EP3, and EP4 receptor antagonists, produced similar effects to the COX-2 inhibitors on cell proliferation and down-regulation of kinetochore/centromere proteins, suggesting that the effect of the COX-2 inhibition is through inactivation of the EP1 receptor signaling. CONCLUSIONS: Our studies indicate that inhibition of COX-2 can arrest prostate cancer cell cycle progression through inactivation of the EP1 receptor signaling and down-regulation of kinetochore/centromere proteins.
Assuntos
Centrômero/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Cinetocoros/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Autoantígenos/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Centrômero/metabolismo , Proteína Centromérica A , Proteínas Cromossômicas não Histona/genética , Ciclo-Oxigenase 2/fisiologia , Regulação para Baixo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Cinetocoros/metabolismo , Masculino , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Fosfatidilinositol 3-Quinases/fisiologia , Neoplasias da Próstata/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Receptores de Prostaglandina E Subtipo EP1/fisiologiaRESUMO
There have been only 2 reported cases of new-onset ulcerative colitis in pediatrics following acute coronavirus disease 2019 (COVID-19). We are reporting a case series of 3 adolescent female patients, 2 of whom were vaccinated against COVID-19, who developed new-onset ulcerative colitis following a recent diagnosis of COVID-19 infections at a singular pediatric hospital. This case series should be an impetus to clinicians who have pediatric patients with persistent symptoms of hematochezia, diarrhea, and abdominal pain following acute COVID-19 infection to consider further workup for inflammatory bowel disease.