Nuclear factor erythroid-2-related factor 2 (Nrf2) is a critical cell protector by inducing phase two detoxifying and anti-oxidant enzymes in normal cells. But recently, numerous evidence show Nrf2 may play the same beneficial roles toward the cancer cells. Nrf2 is found upexpressed in lots of cancers and promote the proliferation and drug resistance. But studies about the role of Nrf2 in the metastases are few. It has been testified that the tumor cells are under hypoxic conditions. As an important anti-oxidant element, the expression of Nrf2 may be upregulated, which in turn promotes the tumor invasion and metastases in the hypoxic microenvironment. Our team found the expression of Nrf2 correlated with the lymph node metastasis of esophageal squamous cell carcinoma by pathological sections of esophageal carcinoma patients. Further, the mechanism beneath it was studied in this paper. It was hypothesized that the hypoxia microenvironment transformed Nrf2 a friend to a foe. First, Eca-109 cells were treated with different concentration of CoCl2 . Western blot and quantitative reverse transcription-polymerase chain reaction showed that with the increase of the concentration of CoCl2 , the expression levels of Nrf2 and hypoxia-inducible factor-1 (HIF-1) alpha were upregulated simultaneously. By analyzing the data, a significant correlation between Nrf2 and HIF-1 alpha in the protein levels was found. Further, blockage of Nrf2 mediated by shRNA suppressed the expression of HIF-1 alpha, hemeoxygenase-1 (HO-1), and matrix metalloproteinase 2 but enhanced the expression of E-cadherin. In addition, the results of wound healing and invasion assay-verified blockage of Nrf2 suppressed the migration and invasion. So it was suggested that blockage of Nrf2 repressed the migration and invasion of esophageal squamous cell carcinoma cells in the hypoxic microenvironment. HIF-1 alpha might be one of the downstream genes of Nrf2 regulated through Nrf2/HO-1 axis in the CoCl2 model. Nrf2 inhibition suppressed matrix metalloproteinase 2 and enhanced E-cadherin partly through HIF-1 alpha way.

BackgroundRadical resection is an effective therapeutic method to increase the survival rate of patients with gallbladder cancer (GBC). In addition to the surgical approach, the relationships between various clinicopathologic factors and the outcome of patients with GBC remain controversial.MethodsClinical and laboratory examination characteristics, pathological and surgical data, and post-operative survival time of 338 patients with advanced GBC who received treatment at the First Affiliated Hospital of Xi'an Jiaotong University, China from January 2008 to December 2012 were analyzed retrospectively. Factors influencing the prognosis of GBC after surgery were analyzed by univariate and multivariate analysis.ResultsThe overall survival rates for curative resection patients were significantly greater than those for non-curative resection patients (1-,3-,5-year survival rate and mean-survival time: 59.0%, 47.3%, 44.3% and 22.0 months vs. 12.7%, 8.3%, 7.7% and 3.0 months) (P < 0.001). For the curative resection patients, positive margin, lymph node metastasis, poorly pathological differentiation and the presence of ascites were all independent risk factors for poor prognosis. For patients with T3 stage, neither segmentectomy of IVb and V nor common bile duct resection improved the prognosis (P = 0.867 and P = 0.948). For patients with T4 stage, aggressive curative resection improved the prognosis (P = 0.007).ConclusionsAn advanced T stage does not preclude curative resection. Positive margin, lymph node metastasis, poorly pathological differentiation and the presence of ascites are all independent risk factors for poor prognosis in the curative intent resection patients. The range of liver resection and whether common bile duct resection is performed do not influence the prognosis as long as R0 resection is achieved.