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Inicio Medicina Clínica (English Edition) A small-molecule antagonist of CXCR1 and CXCR2 inhibits cell proliferation, migr...
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Vol. 152. Issue 11.
Pages 425-430 (June 2019)
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Vol. 152. Issue 11.
Pages 425-430 (June 2019)
Original article
DOI: 10.1016/j.medcle.2018.08.016
A small-molecule antagonist of CXCR1 and CXCR2 inhibits cell proliferation, migration and invasion in melanoma via PI3K/AKT pathway
Una molécula pequeña antagonista de CXCR1 y CXCR2 inhibe la proliferación, migración e invasión celular en el melanoma a través de la vía PI3K/AKT
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Fu-min Shanga, Jing Lib,
Corresponding author
lijing810222@126.com

Corresponding author.
a Department of Dermatology, Shandong Provincial Xintai People's Hospital, Xintai, Shandong, PR China
b Department of Dermatology, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, PR China
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Abstract
Introduction

Melanoma is the most dangerous skin cancer with high metastasis rate and mortality. Although the emergence of immunotherapy has brought hope for treatment, the mortality rate of melanoma is still increasing year by year. The underlying mechanism of melanoma tumor progression and metastasis is urgently needed to be clarified. Recently chemokines have been found to play an important role in tumor progression in addition to their immunocytochemical chemotaxis.

Methods

In this study, human melanoma cell lines A375 and M14 were treated with SCH-527123, a small molecule antagonist of CXCR1 and CXCR2. The effects of treatment with SCH-527123 on melanoma cell proliferation, migration and invasion were evaluated in vitro by CCK-8, colony formation and transwell assays. Apoptosis was also detected by flow cytometry staining with annexin V and propidium iodide (PI). The molecular mechanisms of antagonist mediated were detected by western blot.

Results

The results showed that SCH-527123 inhibited the proliferation, migration and invasion of melanoma cell lines and promoted apoptosis. The expression of CXCR1 and CXCR2 was downregulated after treatment with SCH-527123. PI3K/AKT pathway and downstream signaling were also inhibited at molecular level owing to treated with SCH-527123.

Conclusion

In conclusion, our study demonstrated that SCH-527123, a small-molecule antagonist for CXCR1 and CXCR2 inhibited cell proliferation, migration and invasion in melanoma via PI3K/AKT pathway.

Keywords:
Melanoma
Proliferation
Migration
Invasion
CXCR1
CXCR2
SCH-527123
Resumen
Introducción

El melanoma es el cáncer de piel más peligroso, con una alta tasa de metástasis y mortalidad. Aunque la inmunoterapia ha traído esperanza para el tratamiento, la tasa de mortalidad del melanoma sigue aumentando año tras año. Es de crucial importancia aclarar el mecanismo subyacente de la evolución y la metástasis del melanoma. Recientemente se ha descubierto que las quimiocinas juegan un importante papel en la evolución tumoral.

Métodos

En el presente estudio, las líneas celulares de melanoma humano A375 y M14 se trataron con SCH-527123, un inhibidor de molécula pequeña de CXCR1 y CXCR2. Los efectos del tratamiento con SCH-527123 sobre la proliferación, migración e invasión de células de melanoma se evaluaron in vitro mediante CCK-8, formación de colonias y ensayos Transwell. También se detectó apoptosis mediante citometría de flujo con tinción con anexina V y yoduro de propidio (PI). Los mecanismos moleculares del antagonista fueron detectados por Western blot.

Resultados

Los resultados mostraron que SCH-527123 inhibió la proliferación, migración e invasión de líneas celulares de melanoma y promovió la apoptosis. La expresión de CXCR1 y CXCR2 disminuyó después del tratamiento con SCH-527123. La vía de señalización de la PI3K/AKT también se inhibió a nivel molecular debido a que se trataron con SCH-527123.

Conclusión

Nuestro estudio demostró que SCH-527123, un inhibidor de molécula pequeña para CXCR1 y CXCR2 inhibió la proliferación celular, la migración y la invasión del melanoma a través de la vía PI3K/AKT.

Palabras clave:
Melanoma
Proliferación
Migración
Invasión
CXCR1
CXCR2
SCH-527123

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