RESUMO
OBJECTIVE: Lung cancer, which is typically diagnosed at later stages, is a leading cause of cancer death among both males and females given its highly invasive and rapidly metastasizing nature. Rho GTPase activating protein 15 (ARHGAP15) is a member of the RhoGAP family and functions in multiple biological processes, such as cell proliferation and migration. However, the effect of ARHGAP15 in lung cancer and its underlying molecular mechanisms remain unclear. PATIENTS AND METHODS: In this study, immunohistochemistry and Real Time PCR were performed to detect ARHGAP15 expression in lung cancer tissues and cells. Proliferation, transwell, and Western blot assays were further performed to explore the role and underlying mechanism of ARHGAP15 in lung cancer. RESULTS: Reduced ARHGAP15 expression was observed in lung cancer tissues and cells. In vitro upregulation of ARHGAP15 in lung cancer cells strongly suppressed cell proliferation, migration, and invasion and was accompanied by reduced matrix metalloproteinase-2 (MMP2), MMP9, vascular endothelial growth factor (VEGF) expression, and the phosphorylation of the signal transducer and activator of transcription-3 (p-STAT3). In contrast, interleukin-6 (IL-6) had the opposite effect and the induction of IL-6 was counteracted by ARHGAP15 upregulation. In addition, the proliferation, migration, and cell invasion induced by ARHGAP15 silencing were potentially inhibited by the STAT3 inhibitor AG490 (100 µM), MMP2, MMP9, VEGF, and p-STAT3 levels decreased. CONCLUSIONS: These results suggest that ARGFAP15 suppressed the proliferation and metastasis of lung cancer cells, which may occur through the inhibition of MMP2, MMP9, and VEGF expression via the STAT3 pathway inactivation.
Assuntos
Proteínas Ativadoras de GTPase/metabolismo , Neoplasias Pulmonares/metabolismo , Fator de Transcrição STAT3/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteínas Ativadoras de GTPase/antagonistas & inibidores , Proteínas Ativadoras de GTPase/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos , Tirfostinas/farmacologiaRESUMO
The biodegradability and biocompatibility of a chitosan film were investigated in mice. The results showed that chitosan films had a mild inflammatory reaction in the early days of grafting, and after 16 weeks the inflammation basically subsided. Chitosan films were easily biodegraded. Chitosan is a novel natural absorbable medical film material and has a good developmental prospect.
Assuntos
Materiais Biocompatíveis , Quitina , Animais , Materiais Biocompatíveis/farmacocinética , Biodegradação Ambiental , Quitina/farmacocinética , Masculino , Teste de Materiais , Membranas Artificiais , CamundongosRESUMO
By immunocytochemical method and radioimmunoassay, the gastrin secreting cells (G cells) and gastrin concentration in antral mucosa, gastric juice and serum in 20 patients with duodenal ulcer (DU) were studied. The number of G cells and gastrin concentration in antral mucosa showed no significant difference as compared with normal control. The number of G cells in patients with DU and antral atrophy was much higher than those with antral atrophy but with DU. It indicated that G cells were increased in number in DU, and the gastrin concentration in gastric juice (271.11 +/- 255.25 pg/ml) was much higher than in sera (74.71 +/- 43.07 pg/ml). G cells were distributed in different parts of pyloric glands, showing that gastrin in gastric juice should come directly from G cells. The disturbance of feedback mechanism in regulating gastric acidity might be an important role in hypersecretion of gastric acid in DU. The increase of gastrin concentration in gastric juice might be closely related to hyperplasia of parietal cells.
