RESUMO
The radioresistance of esophageal squamous cell carcinoma (ESCC) remains an obstacle for the effective radiotherapy of ESCC. This study aimed to investigate the radiosensitization of ESCC by signal transducer and activator of transcription 3 (STAT3) inhibitor stattic. ECA109, TE13, and KYSE150 cell lines were exposed to hypoxia and treated with stattic or radiation, alone or in combination. Cell proliferation, colony formation, apoptosis, and double-stranded DNA breaks (DSBs) were examined. In addition, ECA109 cells were xenografted into nude mice and treated with radiation and/or stattic. The levels of STAT3, p-STAT3, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) in ESCC cells and xenografts were detected by Western blot and immunohistochemical analysis. Our results showed that stattic efficiently radiosensitized ESCC cells and xenografts, especially under hypoxia. Moreover, stattic inhibited STAT3 activation and downregulated HIF-1α and VEGF expression. In conclusion, stattic confers radiosensitivity in ESCC cells in vitro and in vivo and is a potential adjuvant for the radiotherapy of ESCC in the clinical setting.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Óxidos S-Cíclicos/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Tolerância a Radiação/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/ultraestrutura , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Regulação para Baixo/efeitos dos fármacos , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/ultraestrutura , Carcinoma de Células Escamosas do Esôfago , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fator de Transcrição STAT3/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Purpose: This retrospective observational study was conducted to determine the correlations between serum CXCL9/12 and the severity of acute ischemic stroke (AIS). Methods: Total 138 patients with AIS were enrolled in the study. These patients underwent Brain CT on admission and blood samples were collected. Serum CXCL9 and CXCL12 were detected by ELISA assay. The correlations of serum CXCL9/12 with AIS was analyzed based on Oxfordshire Community Stroke Project (OCSP) classification, Trial of Org 10,172 in acute stroke treatment (TOAST) classification, National Institutes of Health Stroke Score (NIHSS) score, infarct volume, and modified Rankin scale (mRS) score. Results: Compared with the controls, patients with AIS had higher levels of serum CXCL9 and CXCL12. Logistic regression analysis determined that CXCL9 and CXCL12 were independent risk factors for AIS. In addition, the increased serum CXCL9 and CXCL12 were associated with TOAST classification, NIHSS score, and infarct volume. However, serum CXCL9 and CXCL12 were not associated with functional outcomes (mRS score). CXCL9 and CXCL12 both exhibited a high diagnostic value in AIS. Conclusion: Serum CXCL9 and CXCL12 were elevated in patients with AIS, closely correlated with the severity of AIS.