| Backgrounds and purpose:Malignant tumor derived from esophageal epithelium called esophagus cancer (carcinoma of the esophagus). Esophagus cancer is a common digestive system malignant tumor. At the same time, esophagus cancer is one of the very poor prognosis of malignant tumor. It is a serious threat to human health. The world has more than200,000people die each year from esophageal cancer,150,000of which in our country, most of esophageal cancer deaths in the world. Esophageal cancer effect of traditional treatment and unsatisfactory, in developing countries more than85percent of the patients with esophageal cancer diagnosed died in two years after diagnosis. In some areas, the incidence of esophageal cancer even occupy the first of a malignant tumor.So far, surgical resection is one of the most commonly used means of solid tumors such as esophageal cancer. But unfortunately, in the surgical removal of the tumor at the same time also brought the body do not tally with the treatment of purpose or even opposite. For a long time, people found that operation can cause tumors to grow. Along with the development of modern medicine, although surgical technique and equipment have made great progress, but when the surgical removal of the tumor caused a large number of tumor cells into the circulation of the blood that there is no significant difference. In addition, even the tumor is very limited, some small tumors are difficult to find before the tumor excision surgery may already exist around the lesion and even the distance. Recently, there is evidence that adrenaline activation can accelerate the growth of tumor. So, for the purpose of treatment of tumor, surgery itself has the potential spread of the sensitive period.Surgery cannot be operated without anesthesia. Clinical commonly used method of anesthesia can impact on cancer outcomes. View of the current study, the anesthesia effect on tumor recurrence metastasis may mainly has two aspects:direct action including affects the invasion and metastasis of tumor cell proliferation, and apoptosis, and indirect effects including immunosuppression.In the surgery for the treatment of malignant tumor, general anesthesia is the most commonly used anesthesia currently. It has exact analgesia, good muscle relaxant, and better controllability. But unfortunately most of the drugs being used in general anesthesia can weaken the body’s immune function that cause negative impact on the tumor therapy. But, during those anesthetic drugs, propofol (2,6-diisopropyl phenol) is one of the few has the anti-tumor effects of general anesthetics. As one of the most commonly used intravenous anesthetic of cancer surgery, propofol has reported has the ability of invasion of the influence of human cancer cells. However, the mechanism is not very clear at present.Extracellular signal regulating kinase (ERK) is a member of mitogen-activated protein kinases (MAPKs) family. It mediated intracellular signal transduction, cell differentiation, growth and development, neural plasticity, and play an important role in many physiological and pathological process. Studies using genetic and pharmacological interference of theRas-ERK pathway have demonstrated that its signals are essential for the maintenance of the transformed phenotype in diverse tumor-derived cells and sophisticated animal models have endorsed the importance of this pathway for tumorigenesis in vivo.In this experiment, we proposed by cultured human esophageal Eca-109cells, to research of propofol on proliferation, invasion and angiogenesis of Eca-109cells. And assuming the above effect through ERK signaling pathway to produce effect.Materials and methods:The human Eca-109cells was treated with propofol at the concentrations of10-100μmol/L for72hours or at the concentration of1100μmol/L for8-72hours. Cell viability was determined by the MTT assay; the effect of propofol on apoptosis by5’-triphosphate-biotin nick end labeling (TUNEL) staining. The effect of propofol on angiogenesis was determined by the chicken chorioallantoic membrane (CAM) angiogenesis assay. The effect of propofol on cell invasion using a modified Matrigel Boyden chamber assay ERK1/2, MMP-9and VEGF leves was detected by western blotting assay.Results:In human Eca-109cells, propofol significantly promoted cell apoptosis and inhibited proliferation in a dose and time-dependent manner. Furthermore, propofol inhibited dose and time-dependent invasion and angiogenesis. Propofol significantly dose and time-dependently down-regulated gene expression and protein production of ERK/pERK, VEGF and MMP-9. The functional effects and MMP-9/VEGF inhibition were shown to be dependent on the ERK/VEGF and ERK/MMP-9signaling pathways.It was noteworthy that the ERK activator (phorbol12-myristate13-acetate [PMA]) treatment increased the MMP-9/VEGF levels after propofol treatment, and led to significant increase of proliferation, invasion and angiogenesis.Conclusions:These findings indicate that propofol inhibited proliferation, invasion and angiogenesis of human Eca-109cells in vitro through modulation of ERK-VEGF/MMP-9signaling. Propofol not only can be an anesthesia agent which reduces pain but plays an important role of inhibiting the migration and angiogenesis of ESCC cells in the therapy of ESCC patients. |
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