ABSTRACT
Lung cancer (LC) is a common cancer with high incidence and mortality rates. In recent years, ginsenoside Rg3 (Rg3), a traditional medicine, is widely used for the treatment of LC. Herein, we concentrate on assessing the effect of Rg3 on LC cell migration and invasion. The effects of Rg3 (0, 25, 50, and 100 µg/ml) on the viability, migration, invasion, angiogenesis, and expressions of epithelial-mesenchymal transition (EMT)-related proteins, cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) of LC cell lines were evaluated by cell counting kit-8 (CCK-8), scratch, transwell, tube formation, and western blot assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess transfection efficiency. COX2 overexpression plasmid and short hairpin RNA for VEGF (shVEGF) were applied to evaluate whether the effect of Rg3 is related to COX2 and VEGF through rescue assay. In this study, Rg3 significantly dose-dependently suppressed the viability, migration, invasion, angiogenesis, and protein expressions of N-cadherin, vimentin, COX2, and VEGF in H1299 and A549 cells, while promoting the expression of E-cadherin protein. COX2 overexpression markedly reversed the effects of Rg3 on the viability, migration, invasion, angiogenesis, and EMT-related protein expression levels in LC cells; however, such effects of COX2 overexpression were offset by VEGF knockdown. In sum, Rg3 alleviates the migration, invasion, and angiogenesis of LC cells by inhibiting the expressions of COX2 and VEGF.
Subject(s)
Ginsenosides , Lung Neoplasms , Humans , Cyclooxygenase 2 , Vascular Endothelial Growth Factor A/metabolism , Cell Line , Ginsenosides/pharmacology , Cell Movement , Lung Neoplasms/metabolism , Epithelial-Mesenchymal Transition , Cell Line, Tumor , Cell ProliferationABSTRACT
After the publication of this work [1].
ABSTRACT
Taking advantage of their enhanced permeability and retention (EPR) effect, nanomedicines have been extensively studied for targeted drug delivery to tumour tissues. However, tumour heterogeneity restricts the EPR effect and drug penetration into tumours, and nanoformulations only generate a limited therapeutic improvement in clinical settings. Macrophages have the inherent ability of tumour homing, stealth in blood circulation, and phagocytosis of particles. In this study, we used peritoneal macrophages as carriers for the delivery of SN38 nanoparticles (SN38-NPs) for cancer treatment. SN38-NPs were internalised by macrophages without any obvious effect on viability and migration, and not only induced apoptosis of tumour cells in vitro, but also accumulated in tumour tissues in vivo. In addition, the macrophage-based delivery system for SN38-NPs showed improved therapeutic effect than an equivalent dose of CPT-11 in an A549 subcutaneous tumour model.
Subject(s)
Drug Delivery Systems , Irinotecan/administration & dosage , Macrophages, Peritoneal/metabolism , Nanoparticles , A549 Cells , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Female , Humans , Irinotecan/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mice , Mice, Inbred ICR , Topoisomerase I Inhibitors/administration & dosage , Topoisomerase I Inhibitors/pharmacology , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: Lung cancer in nonsmokers tends to be driven by a single somatic mutation or a gene fusion. KIF5B-RET fusion is an oncogene identified in non-small cell lung cancers. In this study, we verified the oncogenic activity of KIF5B-RET fusion and investigated how KIF5B-RET activates the specific signaling pathways for cellular transformation. We aimed to provide a basis for the further development of the therapy for KIF5B-RET positive lung cancer patients. METHODS: RT-PCR was used to screen for KIF5B-RET fusions in Chinese lung cancer patients. To verify the oncogenic activity of KIF5B-RET kinase in lung cancer cells, we manipulated its expression genetically followed by colony formation and tumor formation assays. The mechanism by which KIF5B-RET kinase induces proliferation was investigated by western blot, coimmunoprecipitation, and administration of RET, MAPK and STAT3 inhibitors. RESULTS: Our study identified a KIF5B-RET fusion in Chinese NSCLC patients and demonstrated that KIF5B-RET transfected cells showed a significantly increased proliferation rate and colony-forming ability. Furthermore, we found that KIF5B-RET fusion kinase induced multilevel activation of STAT3 at both Tyr705 and Ser727, and KIF5B-RET-STAT3 signaling related inhibitors repressed the proliferation and tumorigenicity of lung cancer cells significantly. CONCLUSIONS: Our data suggest that KIF5B-RET promotes the cell growth and tumorigenicity of non-small cell lung cancers through multilevel activation of STAT3 signaling, providing possible strategies for the treatment of KIF5B-RET positive lung cancers.
