Resveratrol Counteracts Hypoxia-Induced Gastric Cancer Invasion and EMT through Hedgehog Pathway Suppression.

BACKGROUND: Gastric Cancer (GC) is one of the most malignant and lethal tumors worldwide. The hypoxic microenvironment is correlated with GC cell invasion, metastasis and Epithelial-Mesenchymal Transition (EMT). Resveratrol is a compound extracted from various plants, including grapes, berries, and some traditional Chinese medicines. Recently, the anticancer properties of resveratrol against many cancers have been reported in a range of studies. However, the exact mechanism through which resveratrol prevents GC invasion and metastasis under hypoxic conditions remains unclear. OBJECTIVE: The objective of this study is to show to what extent resveratrol could inhibit the hypoxia-induced malignant biological behavior of GC. METHODS: SGC-7901 cells were cultured in a consistent 3% O2 hypoxic condition or 21% O2 normal condition for 48 hours to establish an in vitro hypoxia model. Western blot and qRT-PCR were used to detect EMT markers of SGC- 7901 cells, including E-cadherin, HIF-1a, Vimentin, etc. Transwell Matrigel Invasion Assays were used to test the invasive ability of SGC-7901 cells. The siRNA targeting Gli-1 showed its role in hypoxia-induced EMT and invasion of SGC-7901 cells. RESULTS: Resveratrol was found to significantly decrease HIF-1α protein levels induced by hypoxia in SGC-7901 cells. HIF-1α accumulation was found to promote cell proliferation, migration, and invasive capacities in addition to EMT changes through the activation of the Hedgehog pathway. These effects were found to be reversed by resveratrol. CONCLUSION: Therefore, these data indicate that resveratrol may serve as a potential anticancer agent for the treatment of GC, even in a hypoxic tumor microenvironment.

Prognostic value of fibrinogen and D-dimer-fibrinogen ratio in resectable gastrointestinal stromal tumors.

AIM: To investigate the prognostic value of preoperative fibrinogen concentration (FIB) and D-dimer-fibrinogen ratio (DFR) in gastrointestinal stromal tumors (GISTs). METHODS: The purpose of this study was to retrospectively analyze 170 patients with GISTs who were admitted to our hospital from January 2010 to December 2015. The optimal cutoff values of related parameters were estimated by receiver operating characteristic (ROC) curve analysis. The recurrence free survival (RFS) rate was evaluated using Kaplan-Meier curves. Univariate analysis and multivariate Cox regression models were used to analyze the prognostic factors of GISTs. The relationship between the FIB, D-dimer, DFR, platelet count (PLT), and the clinicopathological features of GISTs was described by the chi-square test or nonparametric rank sum test (Mann-Whitney test). RESULTS: In ROC analysis, the optimal cutoff values of FIB, D-dimer, DFR, and PLT were 3.24 g/L, 1.24 mg/L, 0.354, and 197.5 (× 109/L), respectively. Univariate analysis and the Kaplan-Meier survival curve showed that FIB, D-dimer, DFR, PLT, National Institutes of Health (NIH) risk category, tumor size, tumor location, and mitotic index were significantly relevant to the 3-year and 5-year survival rate of patients (P < 0.05). Cox multivariate regression analysis illustrated that FIB (RR: 0.108, 95%CI: 0.031-0.373), DFR (RR: 0.319, 95%CI: 0.131-0.777), and NIH risk category (RR: 0.166, 95%CI: 0.047-0.589) were independent prognostic factors of the RFS rate (P < 0. 05). Moreover, FIB, D-dimer, DFR, and PLT were correlated with the clinical features of GISTs. CONCLUSION: FIB, D-dimer, DFR, and PLT are all related to the prognosis of GISTs. Moreover, FIB and DFR may be independent risk factors for predicting the prognosis of resectable GISTs.

[Curcumin inhibited hypoxia induced epithelial-mesenchymal transition in hepatic carcinoma cell line HepG2 in vitro].

OBJECTIVE: To explore effects and possible mechanisms of curcumin on hypoxia induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cell line HepG2. METHODS: HepG2 cells were divided to 3 groups, i.e., the normal control group, the CoCl2 group, and the CoCl2 plus 10 micromol/L curcumin group. The proliferation of HepG2 was determined using MTT assay. The migration of HepG2 was detected by wound healing assay.The mRNA expression of hypoxia-inducible factor-1 (HIF-1alpha) was evaluated with real-time RT-PCR. The protein expressions of HIF-1alpha, epithelial-cadherin (E-cadherin), and vimentin were determined using Western blot. RESULTS: Compared with the normal control group, the proliferation and migration of HepG2 cells under CoCl2-induced hypoxia significantly increased, the expression of HIF-1alpha was up-regulated, and the expression of E-cadherin protein was obviously down-regulated, and the expression of vimentin significantly increased (all P < 0.05). Intervention by curcumin significantly inhibited the proliferation and migration of hypoxic HepG2 cells, and expressions of HIF-1alpha and vimentin decreased, and the expression of E-cadherin was up-regulated, showing statistical difference when compared with those of the CoCl2 group (P < 0.05). There was no statistical difference in HIF-1alpha mRNA expression among the 3 groups (P > 0.05). CONCLUSION: Curcumin could reverse the proliferation and migration of HepG2 cells under CoCl2-induced hypoxia condition, which might be associated with inhibiting up-regulated expressions of HIF-1alpha protein and EMT.

Biomarkers screening between preoperative and postoperative patients in pancreatic cancer.

OBJECTIVE: To investigate discriminating protein patterns and potential biomarkers in serum samples between pre/postoperative pancreatic cancer patients and healthy controls. METHODS: 23 serum samples from PC patients (12 preoperative and 11 postoperative) and 76 from healthy controls were analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) technique combined with magnetic beads-based weak cation-exchange chromatography (MB-WCX). ClinProTools software selected several markers that made a distinction between pancreatic cancer patients and healthy controls. RESULTS: 49 m/z distinctive peaks were found among the three groups, of which 33 significant peaks with a P < 0.001 were detected. Two proteins could distinguish the preoperative pancreatic cancer patients from the healthy controls. About 15 proteins may be potential biomarkers in assessment of pancreatic cancer resection. CONCLUSION: MB-MALDI-TOF-MS method could generate serum peptidome profiles of pancreatic cancer and provide a new approach to identify potential biomarkers for diagnosis and prognosis of this malignancy.