RESUMEN
This study aimed to evaluate the biological functions of excision repair cross complementation goup 1 (ERCC1) in cell proliferation, cell cycle, invasion and cisplatin response of non-small cell lung cancer (NSCLC) cells. Firstly, ERCC1 gene was successfully transfected into H1299 cells by gene cloning and transfection techniques. Then, cell proliferation was determined with the cell growth curve and colony-forming assays. Flow cytometry (FCM) was employed to investigate the cell cycle distribution. The ability of cell invasion was estimated by means of Matrigel invasion assays. Response of NSCLC cells to cisplatin was detected utilizing MTT assays, and the intracellular drug concentrations were determined by the high performance liquid chromatography (HPLC) analysis. Expression of the two cell membrane proteins, P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), was also evaluated utilizing FCM technique. By contrast, ERCC1 expression in the NSCLC A549 cells was silenced by small interfering RNA (siRNA) through RNAi technique. In addition, the cytotoxic effect of cisplatin on A549 cells was detected by MTT assays. In the present study, the results demonstrated that ERCC1 had no effect on cell proliferation, cell cycle and the ability of invasion, but showed significant impact on cisplatin response of the NSCLC H1299 cells. Furthermore, siRNA-induced suppression of ERCC1 evidently enhanced sensitivity to cisplatin of NSCLC A549 cells. Therefore, it is confirmed that ERCC1 is a chemotherapy-tolerating gene and a promising predictor in tailoring chemotherapy of NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/administración & dosificación , Proteínas de Unión al ADN/biosíntesis , Endonucleasas/biosíntesis , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Proteínas de Unión al ADN/antagonistas & inhibidores , Resistencia a Antineoplásicos/genética , Endonucleasas/antagonistas & inhibidores , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesis , Invasividad Neoplásica/genética , Pronóstico , ARN Interferente PequeñoRESUMEN
BACKGROUND: To maximize the preservation of functional pulmonary parenchyma and improve the quality of life of patients with centrally located lung cancer, trachea-bronchoplasty has been used in clinical application with good efficacy. The aim of this study is to explore the appropriate admission and management of trachea-bronchoplasty and prevent complications of trachea-bronchial sleeve resection in the treatment of centrally located lung cancer. METHODS: Seventy-six patients with central lung cancer, who were treated with trachea-bronchoplasty from June, 1988 to October, 2004, were analyzed. There were 49 cases of squamous cell carcinoma, 16 adenocarcinoma, 7 adenosquamous carcinoma, 3 small cell lung cancer and 1 adenoid cystic adenocarcinoma. Seventeen patients were in stage I, 39 in stage II, 17 in stage IIIA and 3 in stage IIIB. There were 55 cases of sleeve lobectomy, 12 lobectomy with wedge resection of the main bronchus, 8 big arc resection of superior lobar bronchus-main trachea-lateral wall of trachea, 1 resection of right upper lobe-right main bronchus-carina-lateral trachea and carinal reconstruction. RESULTS: Postoperative complications happened in 7 patients. Pneumonia and atelectasis occurred in 6 cases, in which 1 died of heart and respiratory failure. Another one died of haemorrhage of upside alimentary canal. Seventy-one patients were followed up (93.4%). The 1-, 3-, 5-year survival rate was 82.4% (56/68), 57.8% (26/45) and 41.7% (15/36) respectively. CONCLUSIONS: The trachea-bronchoplasty can not only preserve functional pulmonary parenchyma as much as possible and improve the quality of life of patients, but also provide an operative opportunity to those patients with poor pulmonary function in the treatment of centrally located lung cancer.