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1.
Anticancer Drugs ; 30(9): 925-932, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31517732

RESUMO

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.


Assuntos
Movimento Celular/efeitos dos fármacos , Diterpenos do Tipo Caurano/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias da Vesícula Biliar/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/tratamento farmacológico , Metaloproteinase 9 da Matriz/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Neoplasias da Vesícula Biliar/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
2.
Dig Liver Dis ; 53(1): 107-116, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33046427

RESUMO

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.


Assuntos
Carcinoma Hepatocelular/patologia , Transição Epitelial-Mesenquimal/genética , Neoplasias Hepáticas/patologia , RNA Longo não Codificante/metabolismo , Adulto , Idoso , Animais , Proteínas Reguladoras de Apoptose , Carcinoma Hepatocelular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Proteínas de Ligação a RNA
3.
Int J Oncol ; 55(1): 331-339, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180536

RESUMO

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.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Metformina/farmacologia , Câncer Papilífero da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
5.
Zhonghua Wei Chang Wai Ke Za Zhi ; 15(10): 1027-31, 2012 Oct.
Artigo em Zh | MEDLINE | ID: mdl-23297462

RESUMO

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.


Assuntos
Colectomia/métodos , Laparoscopia , Idoso de 80 Anos ou mais , Fístula Anastomótica , Humanos , Tempo de Internação , Duração da Cirurgia , Resultado do Tratamento
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