BackgroundResveratrol, a natural polyphenolic phytoalexin, has potent anti-tumor activity. Recently, it was found to induce autophagy in cancer cells. However, the effects of resveratrol on autophagy in non-small-cell lung cancer (NSCLC) cells have not yet been clearly elucidated.Materials and methodsA549 and H1299 cells were treated with different concentrations of resveratrol. Cell growth and apoptosis were measured by CCK-8 assay and flow cytometry, respectively. A549 cells were then treated with 200 μM resveratrol or SRT1720. Cell autophagy was detected by western blot and immunofluorescence.ResultsIn this study, we found that resveratrol exerted the anti-tumor effect through inhibiting cell proliferation and promoting cell apoptosis in NSCLC cells dose-dependently. Resveratrol has also increased the relative expression of Beclin1 and LC3 II/I while decreased p62 expression, suggesting that resveratrol induced autophagy in NSCLC cells. In addition, resveratrol increased SIRT1 expression and SIRT1 activator SRT1720-induced autophagy of NSCLC cells. SIRT1 knockdown reduced resveratrol-induced autophagy significantly. These results indicated that resveratrol might induce autophagy through upregulating SIRT1 expression. Moreover, inhibiting autophagy by autophagy inhibitor 3-methyladenine or SIRT1 inhibitor nicotinamide significantly suppressed proliferation while promoted apoptosis compared with the resveratrol 200 μM group, suggesting that resveratrol-induced autophagy might act as a protective mechanism to promote NSCLC cell survival and inhibiting autophagy can enhance the anti-tumor effect of resveratrol. Besides that, resveratrol treatment inhibited Akt/mTOR while p38-MAPK was activated in NSCLC cells in a dose-dependent manner. Activating Akt/ mTOR pathway by IGF-1 or inhibiting p-38-MAPK pathway by doramapimod significantly inhibited cell proliferation while increased cell apoptosis of NSCLC cells compared with the resveratrol 200 μM group.ConclusionTaken together, our findings suggest that resveratrol inhibited proliferation but induced apoptosis and autophagy via inhibiting Akt/mTOR and activating p38-MAPK pathway. Resveratrol-induced autophagy might act as a protective mechanism to promote NSCLC cell survival. Therefore, inhibition of autophagy may enhance the anti-tumor activity of resveratrol in NSCLC.
Measurement of fractional exhaled nitric oxide (FeNO) is a quantitative and non-invasive approach to examine airway inflammation, which is a powerful aid in diagnosing chronic disorders of airways like asthma. Diagnostic value of FeNO and relevant indices on pulmonary function in the patients with asthma and chronic obstructive pulmonary disease (COPD) was evaluated. A total of 164 patients [58 asthma, 49 COPD and 57 asthma-COPD overlap (ACO)] were randomly recruited. FeNO, pulmonary ventilation function, and bronchial diastolic function were performed. Eight indicators including FeNO, vital capacity percentage (VC%), forced vital capacity percentage (FVC%), forced expiratory volume in one second percentage (FEV1%), forced expiratory volume in one second to forced vital capacity percentage (FEV1/FVC%), maximum independent ventilation volume percentage (MVV%), the increased percentage of FEV1 after bronchial diastolic test, the increased absolute value of FEV1 after bronchial diastolic test were examined. Significant difference in VC%, FVC%, FEV1%, FEV1/FVC%, MVV%, the increased absolute value of FEV1 after bronchial diastolic test and FeNO were significantly different between patients with asthma and patients with COPD (P<0.05). There were significant differences of VC%, FVC%, FEV1%, FEV1/FVC%, MVV% and the increased percentage of FEV1 after bronchial diastolic test in cases of patients with asthma compared to ACO patients (P<0.05). There was no statistical significance on VC%, FVC%, FEV1%, FEV1/FVC%, MVV% between COPD patients and ACO patients (P>0.05). However, more importantly, the increased percentage of FEV1 after bronchial diastolic test, the increased absolute value of FEV1 after bronchial diastolic test and the alterations on FeNO were found significantly different in ACO group compared with COPD alone (P<0.05). We compared the results from pulmonary ventilation function, bronchial diastolic function examination as well as FeNO detection among 3 groups of asthma, COPD and ACO. The examination of pulmonary ventilation function and bronchial diastolic function combined with FeNO detection is helpful in the early screening of ACO.
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