Human cytomegalovirus infection enhances 5lipoxygenase and cycloxygenase2 expression in colorectal cancer.
Int J Oncol
; 63(5)2023 11.
Article
en En
| MEDLINE
| ID: mdl-37654195
ABSTRACT
Colorectal cancer (CRC) is one of the most common and fatal types of cancer. Inflammation promotes CRC development, however, the underlying etiological factors are unknown. Human cytomegalovirus (HCMV), a virus that induces inflammation and other cancer hallmarks, has been detected in several types of malignancy, including CRC. The present study investigated whether HCMV infection was associated with expression of the proinflammatory enzymes 5lipoxygenase (5LO) and cyclooxygenase2 (COX2) and other molecular, genetic and clinicopathological CRC features. The present study assessed 146 individual paraffinembedded CRC tissue microarray (TMA) cores already characterized for TP53 and KRAS mutations, microsatellite instability (MSI) status, Ki67 index and EGFR by immunohistochemistry (IHC). The cores were further analyzed by IHC for the expression of two HCMV proteins (Immediate Early, IE and pp65) and the inflammatory markers 5LO and COX2. The CRC cell lines Caco2 and LS174T were infected with HCMV strain VR1814, treated with antiviral drug ganciclovir (GCV) and/or antiinflammatory drug celecoxib (CCX) and analyzed by reverse transcriptionquantitative PCR and immunofluorescence for 5LO, COX2, IE and pp65 transcripts and proteins. HCMV IE and pp65 proteins were detected in ~90% of the CRC cases tested; this was correlated with COX2, 5LO and KI67 expression, but not with EGFR immunostaining, TP53 and KRAS mutations or MSI status. In vitro, HCMV infection upregulated 5LO and COX2 transcript and proteins in both Caco2 and LS174T cells and enhanced cell proliferation as determined by MTT assay. Treatment with GCV and CCX significantly decreased the transcript levels of COX2, 5LO, HCMV IE and pp65 in infected cells. HCMV was widely expressed in CRC and may promote inflammation and serve as a potential new target for CRC therapy.
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Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Infecciones por Citomegalovirus
Límite:
Humans
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2023
Tipo del documento:
Article
País de afiliación:
Suecia