ABSTRACT
AIM:To detect the changes of active status of bypass signaling pathways in EML4-ALK positive lung cancer cell line H3122 treated with alectinib, hepatocyte growth factor (HGF), epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), and to explore the potential mechanisms.METHODS:EML4-ALK positive cell line H3122 was treated with increasing concentrations of alectinib or/and induced by HGF, EGF and TGF-α.The cell viability was measured by CCK-8 assay.The cell apoptosis was analyzed by flow cytometry.The protein levels and phosphorylation status of ALK, c-Met and EGFR, and the downstream molecules AKT, ERK, p-AKT and p-ERK were examined by Western blot.RESULTS:The viability of the H3122 cells was inhibited by alectinib in a dose-dependent manner after administrated for 72 h, and the IC50 value was 0.042 μmol/L.The concentration-growth curves of the H3122 cells shifted to the right after induced by HGF, EGF and TGF-α.After treatment with alectinib at 0.05 μmol/L for 48 h, the apoptotic rate of H3122 cells was (20.12±1.36)%, while the apoptotic rates of the cells in the groups of alectinib combined with HGF, EGF or TGF-α were (7.85±1.03)%, (5.60±0.79)% and (4.58±1.00)%, respectively.Those values were remarkably lower than those in alectinib single treatment group (P<0.05).Alectinib inhibited the protein levels of p-ALK and its downstream signaling pathway molecules, while HGF significantly up-regulated the protein levels of p-Met and its downstream p-AKT and p-ERK.Besides, EGF and TGF-α remarkablely up-regulated the protein levels of p-EGFR and its downstream p-AKT and p-ERK.Combined treatment with crizotinib and 17-DMAG successfully inhibited the viability of the H3122 cells even in the presence of the HGF and EGFR ligands, respectively.CONCLUSION:Bypass signaling pathways are activated by HGF, EGF and TGF-α in EML4-ALK positive lung cancer cell line H3122, which may be linked to alectinib resistance.
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Objective To investigate the protective effects of active components of notoginseng on immunological liver injury in mice. Methods Sixty Kunming mice were randomly divided into normal group (group A), model group (Group B), PNS group (Group C), total flavonoids group (Group D),and polysaccharide group (group E). C,D and E groups were given PNS, total flavonoids and polysaccharide orally, 1/day for 14 days. Then BCG was intravenous injected in B, C, D and E groups, and after 26 days lipopolysaccharide (LPS) was intravenous injected. Samples of eye venous plexus blood were collected, and serum levels of alanine aminotransferase (ALT), total superoxide dismutase (T-SOD) and Interleukin-4 (IL-4) were detected. Organs index was calculated by checking pathological results of liver, spleen and thymus. Results Com-pared with group B, the thymus index and serum ALT levels were significantly decreased in C, D and E groups (P<0.01), but the levels of IL-4 and T-SOD increased significantly (P<0.01). Pathological results showed that there were more serious inflammatory cell infiltration in liver, edema and necrosis of dot in C, D and E groups than those in group B. Conclusion The active components of notoginseng showed a significant protective effect on immunological liver injury.
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Objective Using CT three-dimensional image technique to observe the pulmonary vein stenosis of circumferential pulmonary vein ablation (CPVA) for atrial ifbrillation (AF) on the structure of pulmonary vein before and after radiofrequency ablation. Methods 28 patients with AF who underwent CPVA were followed-up for a mean (6.5±3.9) months.The results of Pulmonary vein morphology study was compared with analysis of preablation, after following up radiofrequency catheter alation (6.5±3.9) months. Pulmonary vein diameters, cross-sectional area and left atrial volume were measured before and after CPVA using 64-slice multidector computed tomography (CT). Results Mild stenosis of pulmonary vein maximum diameter and pulmonary minimum diameter were 61.6%and 56.3%after CPVA. Moderate stenosis of pulmonary vein maximum diameter and pulmonary minimum diameter were 3.6%and 5.4%. All patients does not present symptoms of pulmonary vein stenosis at rest on during excercise during follow up. Conclusions Mild and moderate asymptomatic pulmonary vein stenosis may present in some patients after CPVA.