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The effect and possible mechanism of vincristine on human gastric cancer cell BGC were investigated in in vitro and in vivo experiments. MTS and Hoechst assay was used to evaluate the effects of vincristine on human gastric cancer cell proliferation and apoptosis, respectively. The proliferation of BGC cells was examined by cell proliferation assay; The apoptosis of BGC cells was assayed by Hoechst and flow cytometry; Cell cycle analysis was performed by flow cytometry. The expression level of cell proliferation, cell cycle, and apoptosis related proteins was determined by Western blotting. The treatment effect of vincristine was analyzed in nude mice. MTS and Hoechst assay showed vincristine could inhibit the growth of BGCs and promote the apoptosis of BGCs both in time-dependent and dose-dependent manners. The apoptosis rate of BGCs cells increased gradually and the cell cycle was arrested in G1 phase after treated with vincristine. Vincristine could downregulate the expression of phosphorylated-FAK, FAK, E2F1, CylinE2, CyclinD2, CDK2, CDK6, and activate apoptosis-related protein Caspase-3. Vincristine could suppress the growth of human gastric cancer in nude mice. Vincristine could inhibit the proliferation and induce the G1-arrest of BGC cells through its downregulation of cell proliferation and cell cycle related proteins and it also promotes the apoptosis of BGC cells through the activation of Caspase-3.
RESUMO
<p><b>OBJECTIVE</b>To investigate the protective effect of phosphodiesterase type 5 inhibitors (tadalafil) on the testis following testicular ischemia-reperfusion injury in rats.</p><p><b>METHODS</b>Eighty-four healthy adult male SD rats were randomly and equally divided into groups A (sham operation), B (testicular torsion + low-dose tadalafil), C (testicular torsion + high-dose tadalafil), and D (testicular torsion + placebo). Models were established in the latter three groups by 7200 torsion of the right testis for 2 hours. The animals in groups A and B were treated by gavage with tadalafil at the dose of 0. 5 mg per kg per day, those in group C at 2 mg per kg per day, and those in group D with saline at the same dose. After 3, 7, and 14 days of treatment, the torsioned testes were harvested for evaluation of the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the testis tissue. The pathological changes in the testis were observed under the light microscope.</p><p><b>RESULTS</b>At 3, 7, and 14 days, the SOD activity was (254.46 +/- 7.43), (278.49 +/- 8.33), and (317.99 +/- 3.31) nU/mg prot in group B, and (277.12 +/- 8.80), (309.40 +/- 2.14), and (320.39 +/- 4.72) nU/mg prot in group C, all obviously higher than in D ([223.21 +/- 4.65], [231.45 +/- 4.16] and [248.28 +/- 5.74] nU/mg prot), while the MDA content was lower in the former two groups than in the latter. At 3 and 7 days, the SOD activity was significantly higher and the MDA level significantly lower in group C than in B (both P < 0.01) , while at 14 days, neither showed any remarkable differences between the two groups (P > 0.05). No obvious histopathological change was observed in the testis tissue of group A. At 3 and 7 days, pathological examination of the testis tissue revealed significant differences in the number of seminiferous epithelial layers, testicular histological score, and seminiferous tubule diameter in group B (P < 0.01), but the three indexes at 14 days in group B and at 7 days in group C exhibited no remarkable differences from those at 14 days in group A.</p><p><b>CONCLUSION</b>Tadalafil can alleviate testicular ischemia-reperfusion injury following testis torsion/detorsion in a time- and dose-dependent manner.</p>