RESUMEN
To explore the effects of early region 1A (E1A) carried by superparamagnetic dextran iron oxide nanoparticles (SDION) on the radiosensitivity of human cervical cancer. The xenograft mice with cervical cancer received weekly intratumoral SDION-E1A injection and a subsequent 50-Gy irradiation. The weekly relative tumor volume and the final tumor volume were compared among different experimental groups. p53 and human epidermal growth factor receptor-2 (HER-2)/Neu expression in final tumor tissue was detected by reverse transcription-PCR and Western blot. The relative tumor volume and the final tissue volume in the SDION-E1A group was significantly smaller than that in Sham and SDION-Vector groups at each time points after irradiation (P < 0.05). Exogenous E1A expression by SDION delivery significantly increased p53 expression, but inhibited HER-2/Neu expression in tumor tissue (P < 0.05). The intratumoral delivery of exogenous E1A carried by SDION increases p53 expression but inhibits HER-2/neu expression, and enhances the radiosensitivity of human cervical cancer in xenograft mice.
Asunto(s)
Proteínas E1A de Adenovirus/metabolismo , Nanopartículas/administración & dosificación , Neoplasias del Cuello Uterino/radioterapia , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Proteínas E1A de Adenovirus/química , Proteínas E1A de Adenovirus/genética , Animales , Western Blotting , Terapia Combinada , Dextranos/química , Femenino , Compuestos Férricos/química , Terapia Genética/métodos , Células HeLa , Humanos , Magnetismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/terapiaRESUMEN
Concurrent chemoradiotherapy (CCRT) is recently recommended as the primary and standard treatment modality for cervical cancer. The aim of this study is to investigate the protein biomarkers associated with CCRT sensitivity, so as to better understand the mechanisms underlying CCRT resistance. Fresh tumor tissues from five cases for each group of CCRT-highly sensitive (CCRT-HS) and CCRT-lowly sensitive (CCRT-LS) were analyzed by 2-D electrophoresis coupled with MALDI-TOF-MS, followed by Western blot for four candidate proteins including S100A9, galectin-7, nuclear matrix protein-238 (NMP-238), and heat shock protein-70 (HSP-70). In randomly selected CCRT-HS (n = 60) and CCRT-LS (n = 35) cases, these four differentially expressed proteins were detected by tissue microarray with immunohistochemistry staining to explore the association between these interested proteins and CCRT sensitivity. Nineteen proteins differentially expressed more than four times between two groups were identified. An association was revealed between CCRT sensitivity and increased S100A9 and galectin-7, but decreased NMP-238 and HSP-70 expression (p < 0.001, respectively). Although none of these four protein markers could be used as an independent predictive factor, a recurrence prediction model was generated by combining S100A9, galectin-7, NMP-238, and HSP-70 as a full predictive factor. The proteomic analysis combined with tissue microarray provides us a dramatic tool in predicting CCRT response. The increased expression of S100A9 and galectin-7, but decreased expression of NMP-238 and HSP-70, suggests a significantly increased sensitivity to CCRT in cervical cancer.