Exosomes with low miR-34c-3p expression promote invasion and migration of non-small cell lung cancer by upregulating integrinα2β1

Exosomes play critical roles in regulating various physiological and pathological processes,including immune stimulation,immune suppression,cardiovascular diseases,and cancers.Recent studies show that exosomes that transport specific microRNAs(miRNAs)are involved in tumor development.However,the molecular mechanism by which tumor invasion and migration are regulated by exosomes from non-small cell lung cancer(NSCLC)is not well understood.Here,we show that exosomes shuttling low levels of miR-34c-3p are involved in NSCLC progression.Our results showed that exosomes derived from NSCLC cells carrying low levels of miR-34c-3p could be transported into the cytoplasm of NSCLC cells and accelerate NSCLC invasion and migration by upregulating integrinα2β1.A luciferase assay revealed that integrinα2β1 was the direct target of miR-34c-3p,and overexpression of integrinα2β1 could promote the invasion and migration of NSCLC cells.The analysis of exosomes derived from clinical serum samples indicated that the expression of miR-34c-3p was significantly downregulated in exosomes from NSCLC patients compared with that of normal controls.A549-derived exosomes promoted NSCLC cells lung metastases in vivo.Exosomes shuttling low levels of miR-34c-3p were associated with the progression of NSCLC in vitro and in vivo.Our data demonstrate that exosomes shuttling low levels of miR-34c-3p can accelerate the invasion and migration of NSCLC by upregulating integrinα2β1.MiR-34c-3p can be a diagnostic and prognostic marker for NSCLC.High expression of integrinα2β1 is positively related to the migration and metastasis of NSCLC cells.

Dehydrocostus lactone exerts the antitumor effect in non-small cell lung cancer H1299 cells

Background:Dehydrocostus lactone(DHC),a sesquiterpene lactone derived from Aucklandiae Radix,has been proved to possess various pharmacological activities.Recently,studies have reported that DHC has potential antitumor activity.However,few studies have reported the effect of DHC on non-small cell lung cancer(NSCLC).Here,we investigated the antitumor effect of DHC in NSCLC H1299 cells.Methods:MTT assay and colony formation assay was used to assess the anti-proliferation effects of DHC in H1299 cells.Wound healing and Transwell assays were utilized to determine the inhibitory effects of migration and invasion,respectively.Apoptosis was detected using the Annexin V/propidium iodide test.Real-time-quantitative PCR(RT-qPCR)was used to detect the mRNA expression level.Results:We demonstrated here that DHC inhibited the proliferation,migration and invasion of H1299 cells in a dose-or time-dependent manner.Additionally,after treating with DHC at the concentration of 32.0μM,the apoptosis of H1299 cells was significantly induced.Moreover,DHC affected the mRNA expression of E-cadherin,N-cadherin,Snail,c-Myc,integrinα2,Survivin and matrix metalloproteinase 2.Conclusion:To summarize,our data support that DHC can inhibit proliferation,invasion,migration and induced apoptosis of NSCLC H1299 cells.DHC should be considered for its potential for adjuvant therapeutic development.

A Study on the Mechanism of Bruceine D in the Treatment of Non-small Cell Lung Cancer H1299 Cells

Background:Non-small cell lung cancer(NSCLC)is considered one of the leading causes of cancer-related death.Despite the availability of drugs for the treatment of NSCLC,the need for the development of novel agents with high efficiency and fewer adverse effects remains unmet.The natural compound bruceine D(BD)is widely recognized for its notable anti-inflammatory,antiparasitic,and hypoglycemic activities.However,it is unclear whether BD can be used as a novel agent for NSCLC treatment.Materials and Methods:MTT and colony formation assays were used to assess the antiproliferative effect of BD on NSCLC cells.Wound healing and transwell assays were performed to determine the effect of BD on the migration and invasion of H1299 cells,respectively.Western blotting assay was used to detect the expression levels of proteins.Results:We demonstrated that BD significantly inhibited the proliferation of H1299,A549,and H226 cells with respective IC50 values of 6.06±0.52,7.15±0.90,and 7.21±0.75μM.In addition,BD suppressed colony formation of H1299 cells in a dose-dependent manner.Following treatment with BD,the migration and invasive capabilities of H1299 cells were significantly inhibited in a dose-and time-dependent manner.Moreover,the results of Western blotting demonstrated that BD treatment resulted in the upregulation of the protein expression of E-cadherin and downregulation of the expression of N-cadherin,twist,snail,integrinαv,integrinβ4,matrix metalloproteinase-7,andβ-catenin proteins.Conclusion:BD inhibits proliferation,migration,and invasion of NSCLC cells;therefore,BD may be considered for its potential in adjuvant therapy for NSCLC.