RESUMEN
Hypoxia has crucial roles in cancer development and progression. Our previous study indicated that cell migration was increased in a hypoxic microenvironment in GBC-SD gallbladder cancer (GBC) cells. Oridonin, a bioactive diterpenoid compound that is isolated from the plant Rabdosia rubescens, has been identified as an anticancer agent in various types of cancer. However, its roles in cell proliferation, apoptosis, and migration in a hypoxic microenvironment and the associated regulatory mechanisms have not yet to be fully elucidated in GBC. The present study investigated the effect of oridonin on cell proliferation, apoptosis, the cell cycle and cell migration in GBC in vitro and in vivo. Furthermore, the role of oridonin in hypoxia-induced cell migration and its underlying mechanisms were explored in GBC. The results indicated that treatment with oridonin significantly suppressed cell proliferation and the metastatic ability of GBC-SD cells in a dose-dependent manner, increased the level of cell apoptosis and induced cell cycle arrest at the G0/G1 phase. Further experiments demonstrated that oridonin could inhibit hypoxia-induced epithelial-mesenchymal transition and cell migration by downregulating the expression levels of hypoxia-inducible factor (HIF)-1α/matrix metallopeptidase (MMP)-9. In addition, oridonin suppressed GBC cell growth and downregulated the expression levels of HIF-1α and MMP-9 in a GBC-SD cell xenograft model. Taken together, these results suggest that oridonin possesses anticancer properties in GBC. Notably, oridonin can suppress tumor epithelial-mesenchymal transition and cell migration by targeting the HIF-1α/MMP-9 signaling pathway.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Diterpenos de Tipo Kaurano/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hipoxia/tratamiento farmacológico , Metaloproteinasa 9 de la Matriz/metabolismo , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Neoplasias de la Vesícula Biliar/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Hipoxia/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
OBJECTIVE: To reveal the effect of lncRNA miR503HG on epithelial-mesenchymal transition (EMT) and angiogenesis in hepatocellular carcinoma (HCC). METHODS: The expressions of miR503HG, miR-15b and PDCD4 in HCC tissues and cell lines were measured. After cell transfection, Transwell assay tested the migration and invasion ability of HCC cells. qRT-PCR and Western blot detected the expressions of EMT markers (E-cad, N-cad, Vim and Snail-1). Matrigel-based tube formation assay assessed the angiogenesis capacity of human umbilical vein endothelial cells (HUVECs) cultured in conditioned medium of treated HCC cells. ELISA detected the level of VEGF in supernatant of HUVECs. RIP, RNA pulldown and dual-luciferase reporter assay were applied to verify the binding of miR-15b to miR503HG or PDCD4. pcDNA3.1-miR503HG-BEL-7404 cells or pcDNA3.1-BEL-7404 cells were implanted into nude mice for construction of HCC model in vivo. RESULTS: miR503HG and PDCD4 were under-expressed and miR-15b was over-expressed in HCC cells and tissues. Up-regulation of miR503HG and PDCD4 or inhibition of miR-15b hindered migration, invasion and EMT of HCC cells and angiogenesis of HUVECs. Both miR503HG and PDCD4 could bind to miR-15b. Over-expression of miR503HG suppressed HCC growth and angiogenesis in nude mice. CONCLUSION: LncRNA miR503HG suppresses EMT and angiogenesis in HCC via miR-15b/PDCD4 axis.
Asunto(s)
Carcinoma Hepatocelular/patología , Transición Epitelial-Mesenquimal/genética , Neoplasias Hepáticas/patología , ARN Largo no Codificante/metabolismo , Adulto , Anciano , Animales , Proteínas Reguladoras de la Apoptosis , Carcinoma Hepatocelular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Proteínas de Unión al ARNRESUMEN
Thyroid cancer is among the most common types of malignant tumor of the endocrine system. The role of metformin in the inhibition of cancer cell proliferation and induction of apoptosis is widely accepted. The present study explored the effect and the underlying mechanisms of metformin on human thyroid cancer TPC1 cells. Following treatment of TPC1 cells with different concentrations of metformin, cell proliferation and apoptosis were analyzed by cell counting kit8 (CCK8) assay and flow cytometry, respectively. Reverse transcriptionquantitative PCR and western blotting were used to detect alterations in the mRNA and protein expression levels, respectively, for heat shock protein family A member 5 (HSPA5, also known as Bip), DNA damageinducible transcript 3 (DDIT3, also known as CHOP) and caspase12. The results demonstrated that treatment with metformin inhibited proliferation and induced apoptosis in a concentration and timedependent manner. In addition, treatment with metformin increased the expression of Bip, CHOP and caspase12 in vitro, activating endoplasmic reticulum (ER) stress. Thapsigargin treatment enhanced the apoptosis induced by metformin. Inhibition of ER stress by 4phenylbutyrate reversed the metformininduced apoptosis. Finally, treatment with metformin inhibited thyroid cancer growth and increased the expression of Bip and CHOP in a TPC1 cell xenograft model. These results indicated that metformin increased the apoptotic rate of thyroid cancer cells via ER stressassociated mechanisms.
Asunto(s)
Estrés del Retículo Endoplásmico/efectos de los fármacos , Metformina/farmacología , Cáncer Papilar Tiroideo/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patologíaRESUMEN
OBJECTIVE: To compare the clinical safety and efficacy of laparoscopic versus open colorectal resection in octogenarians. Methods Studies comparing laparoscopic colorectal resection with open colorectal resection in octogenarians were identified from the Medline, Embase, Ovid, and Cochrane databases from 1990 to 2012. The methodological quality of the selected studies was assessed to determine studies suitable for inclusion. Meta-analysis was performed by fixed or random effects model. RESULTS: Five observational studies with a total of 685 patients (330 laparoscopic colorectal resections and 355 open colorectal resections) were identified. Laparoscopic colorectal resection was associated with a prolonged operative time (WMD=27.89, P<0.01) and a lower rate of overall complications (OR=0.58, P<0.01), wound infection (OR=0.50, P<0.05), cardiovascular complication(OR=0.53, P<0.05), quicker bowel function return (WMD=-0.83, P<0.01), and shorter length of hospital stay (WMD=-3.60, P<0.05). No differences were found with regard to anastomotic leak (OR=1.13, P>0.05), prolonged ileus (OR=0.71, P>0.05), respiratory complication (OR=0.59, P>0.05),mortality (OR=0.67, P>0.05), and reoperation (OR=0.85, P>0.05). CONCLUSION: Laparoscopic colorectal resection is as safe as open colorectal resection, and is more favorable in terms of length of hospital stay and bowel function return in octogenarians.