RESUMO
BACKGROUND AND OBJECTIVE: Long non-coding RNA, BANCR, has been demonstrated to contribute to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer is still unknown. In present study, we investigated whether BANCR was involved in the development of gastric cancer cells via regulation of NF-κB1. METHODS: Human gastric cancer tissues were isolated as well as human gastric cell lines MGC803 and BGC823 were cultured to investigate the role of BANCR in gastric cancer. RESULTS: BANCR expression was significantly up-regulated in gastric tumor tissues and gastric cell lines. Down-regulation of BANCR inhibited gastric cancer cell growth and promoted cell apoptosis, and it also contributed to a significant decrease of NF-κB1 (P50/105) expression and 3'UTR of NF-κB1 activity. Overexpression of NF-κB1 reversed the effect of BANCR on cancer cell growth and apoptosis. MiroRNA-9 (miR-9) targeted NF-κB1, and miR-9 inhibitor also reversed the effects of BANCR on gastric cancer cell growth and apoptosis. CONCLUSION: BANCR was highly expressed both in gastric tumor tissues and in cancer cells. NF-κB1 and miR-9 were involved in the role of BANCR in gastric cancer cell growth and apoptosis.
Assuntos
Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , NF-kappa B/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Regiões 3' não Traduzidas , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Transplante de Neoplasias , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: In this study, we report the influence of CCL21 and its receptor, CCR7, on the progression of pancreatic cancer and illuminates the correlation between the CCL21/CCR7 axis and the angiogenesis and lymphangiogenesis of pancreatic adenocarcinoma (PAC). METHODS: A total of 30 patients with pancreatic cancer was involved in the current study. The expression of CCL21 and CCR7 in cancerous tissues, paracancerous tissues and normal pancreas were investigated using real-time PCR, Western blot and immunohistochemistry, respectively. In addition, we assessed microvessel density (MVD) and microlymphatic vessel density (MLVD) in tumor tissues using immunohistochemistry. RESULTS: Compared to paracancerous tissues and normal pancreas, CCL21 expression in cancerous tissues was detected at a significantly low level. In contrast, the CCR7 expression was considerably higher in cancerous tissues than in normal pancreas and paracancerous tissues. Additionally, a significant correlation between the expression pattern of the CCL21/CCR7 axis and clinicopathological features, such as lymph node metastasis, was identified. Furthermore, we found that CCL21 expression was significantly associated with MVD but not significantly associated with MLVD, while CCR7 expression was significantly associated with MLVD but not significantly associated with MVD. CONCLUSIONS: The chemotactic interaction between CCR7 and its ligand, CCL21, may be a critical event during progression in pancreatic cancer, and its underlying mechanism may be induction of angiogenesis and lymphangiogenesis regulated by this chemotactic interaction.
Assuntos
Quimiocina CCL21/genética , Linfangiogênese/genética , Neovascularização Patológica/genética , Neoplasias Pancreáticas/genética , RNA Neoplásico/genética , Receptores CCR7/genética , Adulto , Idoso , Western Blotting , Linhagem Celular Tumoral , Quimiocina CCL21/biossíntese , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores CCR7/biossíntese , Estudos RetrospectivosRESUMO
The aim of this study was to investigate induction of apoptosis by the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and gemcitabine in the pancreatic cancer cell line SW1990. The sensitivity of SW1990 cells to TRAIL and/or gemcitabine-induced apoptosis and the rate of apoptosis were assessed by MTT assay and flow cytometry, respectively. We used Hoechst 33342 staining to observe apoptotic morphology and expression levels of proteins were analyzed by Western blottin. Growth inhibition and apoptosis rates on treatment with the combination of TRAIL and gemcitabine were significantly higher than with each drug alone (p<0.05). Pancreatic cancer cells exhibited a typical apoptosis morphology after treatment with TRAIL or gemcitabine. The levels of cellular apoptosis-associated proteins such as Smac/DIABLO, Cyto C, and the activated fragment of caspase-3 (P17) increased, but the expression of XIAP was significantly decreased after 24 h (p<0.05). SW1990 cells responded to TRAIL and/or gemcitabine-induction of apoptosis in a time and concentration-dependent manner. The mechanism of the apoptosis-sensitization effect appeared associated with significant up-regulation of Smac/DIABLO and cytochrome C, down-regulation of XIAP, and activation of caspase-3.