Increased SHP-1 expression results in radioresistance, inhibition of cellular senescence, and cell cycle redistribution in nasopharyngeal carcinoma cellsReportar como inadecuado




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Radiation Oncology

, 10:152

Radiation Biology and Molecular Radiation Oncology

Abstract

BackgroundRadioresistance is the main limit to the efficacy of radiotherapy in nasopharyngeal carcinoma NPC.
SHP-1 is involved in cancer progression, but its role in radioresistance and senescence of NPC is not well understood.
This study aimed to assess the role of SHP-1 in the radioresistance and senescence of NPC cells.

MethodsSHP-1 was knocked-down and overexpressed in CNE-1 and CNE-2 cells using lentiviruses.
Cells were irradiated to observe their radiosensitivity by colony forming assay.
BrdU incorporation assay and flow cytometry were used to monitor cell cycle.
A β-galactosidase assay was used to assess senescence.
Western blot was used to assess SHP-1, p21, p53, pRb, Rb, H3K9Me3, HP1γ, CDK4, cyclin D1, cyclin E, and p16 protein expressions.

ResultsCompared with CNE-1-scramble shRNA cells, SHP-1 downregulation resulted in increased senescence +107 %, P < 0.001, increased radiosensitivity, higher proportion of cells in G0-G1 +33 %, P < 0.001, decreased expressions of CDK4 −44 %, P < 0.001, cyclin D1 −41 %, P = 0.001, cyclin E −97 %, P < 0.001, Rb −79 %, P < 0.001, and pRb −76 %, P = 0.001, and increased expression of p16 +120 %, P = 0.02.
Furthermore, SHP-1 overexpression resulted in radioresistance, inhibition of cellular senescence, and cell cycle arrest in the S phase.
Levels of p53 and p21 were unchanged in both cell lines all P > 0.05.

ConclusionSHP-1 has a critical role in radioresistance, cell cycle progression, and senescence of NPC cells.
Down-regulating SHP-1 may be a promising therapeutic approach for treating patients with NPC.

KeywordsNasopharyngeal carcinoma SHP-1 Cellular senescence Cell cycle distribution p16 Rb AbbreviationsANOVAAnalysis of variance

HP1γHeterochromatin protein-1γ

NPCNasopharyngeal carcinoma

RTRadiotherapy

SDStandard deviation

SNKStudent-Newman-Keuls

Ziyi Sun and Xiaofen Pan contributed equally to this work.

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Autor: Ziyi Sun - Xiaofen Pan - Zhenwei Zou - Qian Ding - Gang Wu - Gang Peng

Fuente: https://link.springer.com/



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