RESUMO
Hepatocellular carcinoma (HCC) is the most common type of liver malignancy with high rates of recurrence and mortality worldwide. Unfortunately, effective strategies for the management of HCC are still unsatisfactory. The aim of this investigation is to explore the effects of catalpol on HCC progression and investigated the mechanistic functions of catalpol in HCC. Catalpol significantly suppressed cell viability, caused the suppression in colony growth, decreased number of invaded and migrated HCC cells, and increased the rates of apoptotic cells and proportions of HCC cells at G0/G1 cell cycle phase. Furthermore, catalpol dramatically up-regulated miR-22-3p expression in HCC cells, and knockdown of miR-22-3p attenuated the anti-tumor effects of catalpol in HCC. Additionally, results from luciferase reporter assay demonstrated that miR-22-3p targeted the metastasis associated 1 family member 3 (MTA3) 3'untranslated region (3'UTR), and miR-22-3p down-regulated MTA3 expression in HCC cells. Overexpression of MTA3 enhanced HCC cell proliferative abilities, increased the number of invasive and migratory HCC cells, and also attenuated the anti-tumor potentials of catalpol in HCC. Catalpol suppressed HCC tumor growth and increased miR-22-3p expression, while down-regulated MTA3 expression in dissected tumor tissues from xenograft nude mice. Collectively, our results for the first time revealed the anti-tumor potentials of catalpol in HCC, and the anti-tumor effects mediated by catalpol were via modulating the miR-22-3p/MTA3 axis in HCC.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glucosídeos Iridoides/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/genética , Proteínas de Neoplasias/genética , Regiões 3' não Traduzidas/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Proteínas de Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Salviae miltiorrhizae radix et rhizoma (Danshen, in Chinese) is one of the traditional Chinese medicines commonly used in clinical practice. In this study, low field nuclear magnetic resonance (LF-NMR) was used to detect changes in the moisture content during the drying of Danshen. Three water states (bound, immobilized, and free) in Danshen were investigated by multi-exponential fitting of the NMR data. Mass changes during drying were analyzed using high-performance liquid chromatography and partial least squares discriminant analysis. The results revealed that two components, salvianolic acid B and tanshinone, were the main chemical substances that produced the differences. Correlations were found among chemical substances, color, and moisture. LF-NMR can quickly assess the moisture content during drying. It also provides a practical tool for the production and processing of medicines or slices.
Assuntos
Rizoma , Salvia miltiorrhiza , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Medicina Tradicional Chinesa , Rizoma/química , Salvia miltiorrhiza/químicaRESUMO
BACKGROUND: Pancreatic cancer is one of the most aggressive malignancies. The present study aimed to examine the anti-tumor effects of honokiol in pancreatic cancer and to explore the underlying molecular mechanisms. MATERIALS AND METHODS: In vitro functional assays determined pancreatic cancer cell proliferation, apoptosis and invasion. Xenograft nude mice model determined the in vivo anti-cancer effects of honokiol. Luciferase reporter assay determined the interaction between miR101 and myeloid cell leukemia-1 (Mcl-1). RESULTS: Honokiol concentration-dependently suppressed pancreatic cancer cell viability. In addition, honokiol increased the caspase-3 activity and cell apoptotic rates, induced cell cycle arrest at G0/G1 phase, and inhibited cell invasion in pancreatic cancer. Interestingly, honokiol treatment induced up-regulation of miR-101 in pancreatic cancer cells. Knockdown of miR-101 attenuated the honokiol-induced cell apoptosis and inhibition in cell invasion of pancreatic cancer cells. On the other hand, miR-101 overexpression induced cell apoptosis and inhibited cell viability and invasion in pancreatic cancer. Further mechanistic study verified that Mcl-1 was negatively regulated by miR-101, and Mcl-1 overexpression counteracted the tumor-suppressive effects of honokiol on the pancreatic cancer cells. In vivo studies showed that honokiol dose-dependently suppressed tumor growth of pancreatic cancer in the nude mice and up-regulated miR-101 expression but down-regulated Mcl-1 expression in tumor tissues. CONCLUSION: Our data showed that honokiol suppressed pancreatic cancer progression via miR-101-Mcl-1 axis. Honokiol could be a promising candidate for cancer prevention and/or therapeutic treatment for pancreatic cancer.