RESUMEN
Lung cancer is the leading cause of cancer mortality worldwide, and the cause of death is metastasis. The epithelial-to-mesenchymal transition (EMT) plays a key role in the process of metastasis. Macrophages within the lung cancer microenvironment release cytokines, such as interleukin-6 (IL-6), and promote lung cancer cell invasion and metastasis. However, the interaction between macrophages and lung cancer cells and the effect of this interaction on the expression of IL-6, EMT, and the invasiveness of lung cancer cells remain unclear. Therefore, we established an in vitro co-culture model of human lung adenocarcinoma A549 or H1299 cells with THP-1-derived macrophages to illuminate the important role of macrophages in the invasion of lung cancer. In this study, we demonstrated that the concentrations of IL-6 in the co-culture supernatants were significantly increased compared with controls. Thus, a complex chemical cross-talk is induced by the indirect cell-to-cell contact between lung cancer cells and THP-1-derived macrophages. THP-1-derived macrophages appeared to play an important initiator role in the process. The analysis of the mRNA expression profiles of the sorted cells from the co-culture system revealed that the co-cultured lung cancer cells are the main source of the observed increase in IL-6 secretion. In addition, the interactions between lung cancer cells and THP-1-derived macrophages are bidirectional. The THP-1-derived macrophages underwent differentiation towards the M2-macrophage phenotype during the co-culture process. The expression of IL-6 was correlated with the induction of EMT, which contributed to a significant increase in the invasiveness of the A549 and H1299 cells in vitro. In addition, the addition of an anti-IL-6 antibody reversed these changes. In summary, we demonstrated that the in vitro co-culture of A549 or H1299 cells with THP-1-derived macrophages upregulates IL-6 expression, which increases the invasion ability of the A549 and H1299 cells through the EMT pathway. The THP-1-derived macrophages that interacted with the lung cancer cells differentiated towards the M2-macrophage phenotype. Thus, the inhibition of IL-6 or of the interactions between lung cancer cells and macrophages may be an effective target for anti-cancer therapy in patients with non-small cell lung cancer.
Asunto(s)
Adenocarcinoma/inmunología , Adenocarcinoma/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Interleucina-6/farmacología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Macrófagos/inmunología , Adenocarcinoma/metabolismo , Adenocarcinoma del Pulmón , Biomarcadores/metabolismo , Línea Celular Tumoral , Técnicas de Cocultivo , Humanos , Interleucina-6/biosíntesis , Neoplasias Pulmonares/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Invasividad Neoplásica , FenotipoRESUMEN
Objective The present study aims to determine the correlation between liver function dam-age and hepatitis B virus ( HBV ) reactivation caused by chemotherapy , and the preventive effect of entecavir on HBV reactivation in lung cancer with HBV carriers .Methods A total of 160 lung cancer patients with HBV car-riers in the affiliated tumor hospital of Harbin Medical University from January 2011 to December 2012 was inves-tigated and the clinical data were studied retrospectively .The patients were divided into prophylactic group ( n=80)and control group(n=80).In prophylactic group,0.5 mg of daily oral entecavir was administered before the chemotherapy until 6 months after the completion of chemotherapy .Control group received no entecavir .The inci-dence of HBV reactivation ,functional damage of liver ,toxicities and disruption of chemotherapy were measured . Results The comparison between the control group (25%) and prevent group (5%) showed a statistically signifi-cant difference in the incidence of HBV reactivation (P0.05).There were significant differences in grade III and IV hepatic toxicity (P0.05).Disruption of chemo-therapy showed significant difference between control group (20%)and prevent group(5%)(P<0.05).The ma-jor grade 1 ~2 toxicities were myelosuppression,nausea,vomiting,skin rash,diarrhoea,neurotoxicity,fatigue, headache,insomnia,etc.All adverse reactions were cured after treatment .Conclusion The prophylactic adminis-tration of oral entecavir could reduce the risk of HBV reactivation in lung cancer with HBV carriers .
RESUMEN
Objective To study human lung adenocarcinoma cell line A-549 treated with antagonist and agonist of potassium channel how to affect metastasis of A-549 and its mechanism. Methods Invasion and migration capability of A-549 in vitro was evaluated by using transwell chamber model. Alteration of cytoskeleton was observed through immunofluorescence. Western blotting were used to detect the protein expression of Ezrin and HuR in A-549 cell lines while Glibenclamde and Pinacidil were applied to them. Results In the presence of the antagonist Glibenclamide, migration of A-549 was inhibited by (57.18±5.46)% and invasion was inhibited by (54.92±3.72)% in the transwell assay, meanwhile A-549 manifested disorder of microtubule and more orderly microfilament. And agonist of the potassium channel had an contrary effect on A-549. Ezrin and HuR protein were successfully down-regulated in A-549 treated with Glibenclamide and upregulated in A-549 treated with pinacidil. Conclusion Functional alterations of the potassium channel affects capability of migration and invision of A-549, which is associated with different expression of ezrin and HuR protein that modify cytoskeleton.