Paraquat-Induced Apoptotic Cell Death in Lung Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Paraquat is extremely toxic chemical material, which generates reactive oxygen species (ROS), causing multiple organ failure. In particular, paraquat leads to irreversible progressive pulmonary fibrosis. Exaggerated cell deaths exceeding the normal repair of type II pneumocytes leads to mesenchymal cells proliferation and fibrosis. This study examined the followings; i) whether or not paraquat induces cell death in lung epithelial cells; ii) whether or not paraquat-induced cell deaths are apoptosis or necrosis; and iii) the effects of N-acetylcysteine, dexamethasone, and bcl-2 on paraquat-induced cell deaths. METHODS: A549 and BEAS-2B lung epithelial cell lines were used. The cell viability and apoptosis were evalluated using a MTT assay, Annexin V staining was monitored by fluorescence microscopy, The level of bcl-2 inhibition was examined by establishing stable A549 pcDNA3-bcl-2 cell lines throung the transfection of pcDNA3-bcl-2 with the mock. RESULTS: Paraquat decreased the cell viability in A549 and BEAS-2B cells in a dose and time dependent manner. The Annexin V assay showed that apoptosis was the type of paraquat-induced cell death. Paraquat-induced cell deaths was significantly inhibited by N-acetylcysteine, dexamethasone, and bcl-2 overexpression. The cell viability of A549 cells treated with N-acetylcysteine, and dexamethasone on the paraquat-induced cell deaths were increased significantly by 10 ~ 20%, particularly at high doses. In addition, the cell viability of A549 pcDNA3-bcl-2 cells overexpressing bcl-2 was significantly higher than the untransfected A549 cells. CONCLUSION: Paraquat induces apoptotic cell deaths in lung epithelial cells in a dose and time dependent manner. The paraquat-induced apoptosis of lung epithelial cells might occur through the mitochondrial pathway.

Concurrent Chemoradiation with Weekly Paclitaxel in Locally Advanced Non-small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Paclitaxel is highly beneficial anticancer drug for the treatment of non-small cell lung cancer and has shown remarkable radiosensitizing effect in vitro. We evaluated whether concurrent chemoradiation therapy with weekly paclitaxel (60 mg/m2) could be tolerated and effective in the treatment of locally advanced non-small cell lung cancer (NSCLC). METHODS: Twenty-two stage III (IIIA:6, IIIB:16) NSCLC patients were treated with weekly administration of paclitaxel (60 mg/m2) on days 1, 8, 15, 22, 29, and 36 in addition to concurrent radiation therapy of 54 Gy. After the initial phase of concurrent chemoradiation, patients received additional two cycles of consolidation chemotherapy with paclitaxel (175mg/m2)/cisplatin (75 mg/m2) or paclitaxel (175 mg/m2)/carboplatin (6AUC) every 3 weeks. RESULTS: Overall response rate was 81.8% (18/22) with 9.1% (2/22) of complete response and 72.7% (16/22) of partial response rate. Two patients (9.1%) died of chemoradiation-induced pneumonitis after completion of therapy. In total, grade 3 toxicities included pneumonitis (22.7%), esophagitis (22.7%), neuropathy (13.6%), and neutropenia (13.6%). The median survival time was 15 months and 2-year overall survival were 31.8%. CONCLUSION: Concurrent chemoradiation therapy with weekly paclitaxel in locally advanced NSCLC showed good local response, but survival rate was not completely satisfactory due to potentially fatal chemoradiati1on-induced pneumonitis.