ABSTRACT
<p><b>OBJECTIVE</b>To explore the intrinsic connection between activation of classical nuclear factor-κB (NF-κB) pathway and gefitinib resistance in human lung adenocarcinoma H1650 cells.</p><p><b>METHODS</b>Human lung adenocarcinoma H1650 cells were exposed to gefitinib continuously for 60 days to obtain resistant H1650 cells. The expressions of P-IκBα, P-p50 and P-p65 in the cytoplasm or nuclei were detected using Western blotting in human lung adenocarcinoma HCC827 cells, parental H1650 cells and gefitinib-resistant H1650 cells. The effects of gefitinib alone or in combination with PDTC on the survival rate and expressions of NF-κB P-p50 and P-p65 were compared among the 3 cell lines.</p><p><b>RESULTS</b>Gefitinib-resistant H1650 cells showed increased cytoplasmic and nuclear P-IκBα expressions. The expressions of P-p50 and P-p65 differed significantly among the 3 cell line, decreasing in the order of resistant H1650 cells, parental H1650 cells, and gefitinib sensitive HCC827 cell lines (P<0.05 or 0.01). Treatment with gefitinib alone resulted in a significantly lower cell inhibition rate in resistant H1650 cells than in the parental H1650 cells (P<0.05) and HCC827 cells (P<0.01). The resistant H1650 cells had a significantly higher expression of P-p50 and P-p65 than other two cell lines (P<0.05). In both the resistant and parental H1650 cells, gefitinib significantly lowered P-p50 and P-p65 expressions (P<0.05 or 0.01), and the combined treatment with gefitinib and PDTC significantly decreased the cell survival rate and further lowered the cytoplasmic and nuclear expressions of P-p50 and P-p65 (P<0.01 or 0.01).</p><p><b>CONCLUSION</b>The activation of classical NF-κB pathway is a key factor contributing to transformation of the parental H1650 cells into gefitinib-resistant cells. Gefitinib combined with PDTC can inhibit P-IκBα production and NF-κB P-p50 and P-p65 activation to suppress the survival of residual H1650 cells and the generation of gefitinib-resistant cells.</p>
ABSTRACT
OBJECTIVE@#To develop a BALB/c mouse model of oral submucous fibrosis (OSF) induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes.@*METHODS@#BALB/c mice were randomly assigned to either the control (distilled water) or experimental group (arecoline) (n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features, levels of collagen type I and collagen type III, and angiogenesis were measured.@*RESULTS@#In the 8th week, epithelium atrophy, collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week, hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type I changed significantly as the diseases advanced (P < 0.05); however, collagen type III was not statistically different.@*CONCLUSIONS@#An OSF model involving mice can be rapidly induced by drinking a high-dose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type I.
ABSTRACT
Objective To develop a BALB/c mouse model of oral submucous fibrosis (OSF) induced by arecoline and to exhibit an accumulation of collagen and angiogenesis changes. Methods BALB/c mice were randomly assigned to either the control (distilled water) or experimental group (arecoline) (n = 40). Eight mice from each group were sacrificed every 4 weeks since 8 weeks post treatment. Changes in histopathologic features, levels of collagen type I and collagen type III, and angiogenesis were measured. Results In the 8th week, epithelium atrophy, collagen cumulation and micrangium pathologic changes in the lamina propria were observed in the oral mucosa. In the 20th week, hyaline degeneration of the connective tissues was observed on the tongue and palate mucosa. The angiogenesis and collagen type I changed significantly as the diseases advanced (P < 0.05); however, collagen type III was not statistically different. Conclusions An OSF model involving mice can be rapidly induced by drinking a high-dose of arecoline. OSF angiogenic changes in mice primarily decrease and collagen accumulation is mainly collagen type I.