[Interleukin 7 and its receptor promote cell proliferation and induce lymphangiogenesis in non-small cell lung cancer].

OBJECTIVE: To study the mechanism of interleukin 7/interleukin 7 receptor (IL-7/IL-7R) in promoting cell proliferation and inducing lymphangiogenesis of non-small cell lung cancer (NSCLC) in vivo and in vitro. METHODS: Immunohistochemical study for IL-7, IL-7R, cyclin D1 and vascular endothelial growth factor-D (VEGF-D) was carried out in NSCLC tissues from 95 patients. The relationship between IL-7/IL-7R expression and various parameters was analyzed. The mechanism of IL-7/IL-7R in promoting cell proliferation and inducing lymphangiogenesis was studied by methylthiazolyldiphenyl-tetrazolium bromide, fluorescence-activated cell sorting, reverse transcriptase-PCR, Western blot, co-immunoprecipitation, chromatin immunoprecipitation and nude mice experiments with xenograft tumors. RESULTS: IL-7 (63.2%, 60/95), IL-7R (61.1%, 58/95), cyclin D1 (52.6%, 50/95) and VEGF-D (58.9%, 56/95) showed that high level of expression in NSCLC. IL-7/IL-7R over-expression correlated with cyclin D1 expression (P < 0.01, P < 0.01), VEGF-D expression (P < 0.01, P < 0.01), increased lymphovascular density (P = 0.005, P = 0.013), advanced clinical stage (P = 0.008, P = 0.005) and presence of lymph node metastasis (P < 0.01, P < 0.01). IL-7/IL-7R could promote proliferation of A549 cell, increase cyclin D1 and VEGF-D expression, and enhance c-Fos/c-Jun expression and phosphorylation, resulting in formation of heterodimer. Furthermore, IL-7/IL-7R could induce binding of c-Fos/c-Jun to cyclin D1/VEGF-D promoters and regulate their transcription. IL-7/IL-7R could also promote proliferation and lymphangiogenesis of lung cancer xenograft tumors. CONCLUSIONS: IL-7/IL-7R promotes c-Fos/c-Jun expression and activity in NSCLC. This further facilitates cyclin D1 expression and accelerates proliferation of cells and VEGF-D-induced lymphovascular formation.

[The effect of simvastatin on alveolar epithelial cells in cigarette smoking-induced emphysema].

OBJECTIVE: to explore the effect of simvastatin on alveolar epithelial cells and the expression of vascular endothelial growth factor (VEGF) in cigarette smoking-induced emphysema in rats. METHODS: twenty-four, 12-week-old healthy male and female Wistar rats were randomly divided into 4 groups of 6 each: a control (W) group, a smoking (Sm) group, a simvastatin (St) group, and a smoking-simvastatin (SmSt) group. The rats were simultaneously fed, and kept in individual cages for 16 weeks. The VEGF level in lung tissue and bronchoalveolar lavage fluid (BALF) of each group was measured by ELISA. The expression of VEGF mRNA was determined by RT-PCR. The expressions of VEGF and proliferating cell nuclear antigen (PCNA) were determined by two-step immunohistochemistry assay. One-way ANOVA and LSD-t test were used for statistical analysis. RESULTS: the percentage of PCNA-positively stained alveolar epithelial cells was significantly higher in the SmSt group [(10.3 ± 2.0)%] than in the Sm group [(4.8 ± 0.8)%]. The levels of VEGF in BALF and lung tissue homogenate of the SmSt group [(187 ± 15) ng/L and (6782 ± 50) ng/L] were similar to the W group [(200 ± 20) ng/L and (7558 ± 330) ng/L], but were significantly higher than that in the Sm group [(71 ± 16) ng/L and (4149 ± 110) ng/L]. VEGF expression in alveolar and bronchial epithelial cells of rats in the SmSt group [(67.7 ± 5.0)% and (49.0 ± 3.0)%], was similar to the W group [(68.3 ± 3.3)% and (51.3 ± 2.9)%]. But the level of VEGF expression was significantly increased as compared to that in the Sm group [(27.0 ± 5.9)% and (16.3 ± 2.7)%]. SmSt group vs Sm group t = 1.117 - 12.001, all P < 0.01. CONCLUSIONS: simvastatin ameliorated the development of cigarette smoke-induced COPD in rats, partly by promoting alveolar epithelial cell proliferation and up-regulating the expression of VEGF.

[Effects of varglaucocalyx on c-fos gene expression during global myocardial ischemia-reperfusion in rat].

OBJECTIVE: To determine the effects of Varglaucocalyx on c-fos gene expression during global myocardial ischemia-reperfusion. METHOD: Forty Wistar rats were divided into 5 groups: group N as control; group CN as ischemia-reperfusion control and group XH, XM and XL treated with Varglaucocalyx 5%, 1%, 0.5% respectively prior to ischemia-reperfusion. The isolated rat hearts were perfused in condition of constant temperature and pressure, and then the left ventricular myocardiums were extracted for use. The expression of c-fos protein was detected by immunochemical method. The expression of c-fos protein were quantified by using computer image analysis system. RESULT: Compared with the values of group N, protein expressions relative area of c-fos gene (PERA) were increased significantly in group CN, XH, XM, XL(P < 0.01), but decreased significantly in group XH, XM, XL, compared with those of group CN (P < 0.05). The PERA of c-fos gene in group XM, XL were significantly lower than in group XH (P < 0.01), and the PERA of c-fos gene in group XM were lower than in group XL(P < 0.05). CONCLUSION: Varglaucocalyx can effectively depress the expression of c-fos gene in myocardium which may account for its protection against myocardial ischemia-reperfusion injury, and the middle and the low concentrations of Varglaucocalyx are more effective than the high concentrations.