BackgroundHepatocellular carcinoma (HCC) is a commonly occurring liver malignancy. Its prognosis remains unsatisfactory. Accumulating evidence has revealed that exosomal microRNAs (miRNAs) act as biomarkers and play crucial roles in the advancement of HCC. The current study explored the biological role and fundamental mechanism of exosomal miR-744 in HCC.Material/MethodsThe serum exosomes of HCC patients were isolated by differential ultracentrifugation. MiR-744 expression in HCC tissues, cell lines and serum exosomes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). EdU (5-ethynyl-2′-deoxyuridine) assay and Cell Counting Kit-8 (CCK-8) assay were conducted to show the impacts of miR-744 or exosomal miR-744 on proliferation and sorafenib resistance in HepG2 cells. The target of miR-744 was ascertained by regulating the level of miR-744 in HepG2 cells.ResultsMiR-744 is downregulated in HCC tissues and cell lines as well as in exosomes derived from patient serum and HepG2 cells. Additionally, downregulated miR-744 promotes HepG2 cell proliferation and inhibits the chemosensitivity of HepG2 cells to sorafenib. PAX2 was identified as the functional target of miR-744. Interestingly, miR-744 is decreased in exosomes derived from sorafenib-resistant HepG2 cells. Furthermore, when treated with the miR-744-enriched exosomes, the proliferation of HepG2 cells was significantly suppressed, and the sorafenib resistance was reduced.ConclusionsMiR-744 has an imperative role in the propagation and chemoresistance of HCC. Serum exosomal miR-744 might act as a biomarker of HCC, and exosomal miR-744 might offer an innovative strategy for HCC treatment.

Hypoxia can induce HIF-1α expression and promote the epithelial-mesenchymal transition (EMT) and invasion of cancer cells. However, their mechanisms remain unclear. The objective of this study was to evaluate the role of Gli-1, an effector of the Hedgehog pathway, in the hypoxia-induced EMT and invasion of breast cancer cells. Human breast cancer MDA-MB-231 cells were transfected with HIF-1α or Gli-1-specific small interfering RNA (siRNA) and cultured under a normoxic or hypoxic condition. The relative levels of HIF-1α, Gli-1, E-cadherin, and vimentin in the cells were characterized by quantitative RT-PCR and Western blot assays, and the invasion of MDA-MB-231 cells was determined. Data was analyzed by Student T test, one-way ANOVA, and post hoc LSD test or Mann-Whitney U when applicable. We observed that hypoxia significantly upregulated the relative levels of vimentin expression, but downregulated E-cadherin expression and promoted the invasion of MDA-MB-231 cells, associated with upregulated HIF-1α translation and Gil-1 expression. Knockdown of HIF-1α mitigated hypoxia-modulated Gil-1, vimentin and E-cadherin expression, and invasion of MDA-MB-231 cells. Knockdown of Gil-1 did not significantly change hypoxia-upregulated HIF-1α translation but completely eliminated hypoxia-modulated vimentin and E-cadherin expression and invasion of MDA-MB-231 cells. These data indicate that Gil-1 is crucial for hypoxia-induced EMT and invasion of breast cancer cells and may be a therapeutic target for intervention of breast cancer metastasis.

Background: Intra-abdominal adhesions are a very common complication following abdominal surgery. Our previous studies have demonstrated that the inhibition of inflammation at the sites of peritoneal injury can prevent the formation of intra-abdominal adhesions. Resveratrol is a natural extract with a broad range of anti-inflammatory effects. Therefore, we propose that resveratrol can reduce the formation of intra-abdominal adhesions after surgery. The aim of this study was to investigate the effect of resveratrol on intra-abdominal adhesion prevention in a rat model with surgery-induced peritoneal adhesions. Materials and Methods: The cecum wall and its opposite parietal peritoneum were abraded following laparotomy to induce intra-abdominal adhesion formation. Varying doses of resveratrol were administered to the animals. On the eighth day after surgery, the adhesion score was assessed using a visual scoring system. Picrosirius red staining and a hydroxyproline assay were used to assess the amount of collagen deposition in the adhesion tissues. The levels of serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and transforming growth factor beta-1 (TGF-β1) were determined by an enzyme-linked immunosorbent assay (ELISA). Western blotting was performed to determine the protein expression of TGF-β1, fibrinogen, and α-smooth muscle actin (α-SMA) in rat peritoneal adhesion tissue. Real-time RT-PCR was performed to quantify the mRNA expression of TGF-β1, fibrinogen, and α-SMA. Results: Resveratrol significantly reduced intra-abdominal adhesion formation and fibrin deposition in the rat model. Furthermore, resveratrol significantly reduced the serum levels of IL-6, TNF-α, and TGF-β1. The protein and mRNA expression of TGF-β1, fibrinogen, and α-SMA in the rat peritoneum and adhesion tissues were also down-regulated due to resveratrol intervention. Conclusion: Resveratrol can effectively prevent the formation of postoperative intra-abdominal adhesions in a rat model. This effect may be related to the suppression of inflammatory cytokine expression in the injured peritoneum by resveratrol. This study suggests that resveratrol may be a new and effective anti-adhesive agent that is worthy of further study and has potential application value.

Tumor cell invasion and metastasis are important processes in colorectal cancer that exert negative effects on patient outcomes; consequently, a prominent topic in the field of colorectal cancer study is the identification of safe and affordable anticancer drugs against cell invasion and metastasis, with limited side effects. Ginkgolic acid is a phenolic acid extracted from ginkgo fruit, ginkgo exotesta and ginkgo leaves. Previous studies have indicated that ginkgolic acid inhibits tumor growth and invasion in a number of types of cancer; however, limited studies have considered the effects of ginkgolic acid on colon cancer. In the present study, SW480 colon cancer cells were treated with a range of concentrations of ginkgolic acid; tetrazolium dye-based MTT, wound-scratch and transwell migration assays were performed to investigate the effects on the proliferation, migration and invasion of colon cancer cells, and potential mechanisms for the effects were explored. The results indicated that ginkgolic acid reduced the proliferation and significantly inhibited the migration and invasion of SW480 cells in a concentration-dependent manner. Additional experiments indicated that ginkgolic acid significantly decreased the expression of invasion-associated proteins, including matrix metalloproteinase (MMP)-2, MMP-9, urinary-type plasminogen activator and C-X-C chemokine receptor type 4, and activated adenosine monophosphate activated protein kinase (AMPK) in SW480 cells. Small interfering RNA silencing of AMPK expression reversed the effect of ginkgolic acid on the expression of invasion-associated proteins. This result suggested that ginkgolic acid inhibited the proliferation, migration and invasion of SW480 colon cancer cells by inducing AMPK activation and inhibiting the expression of invasion-associated proteins.

Background Postoperative intra-abdominal adhesions are a major complication after abdominal surgery. Although various methods have been used to prevent and treat adhesions, the effects have not been satisfactory. Emodin, a naturally occurring anthraquinone derivative and an active ingredient in traditional Chinese herbs, exhibits a variety of pharmacological effects. In our study, we demonstrated the effect of emodin treatment on preventing postoperative adhesion formation. Materials and Methods A total of 48 rats were divided into six groups. Abdominal adhesions were created by abrasion of the cecum and its opposite abdominal wall. In the experimental groups, the rats were administered daily oral doses of emodin. On the seventh day after operation, the rats were euthanized, and blood and pathological specimens were collected. Abdominal adhesion formation was evaluated by necropsy, pathology, immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay analyses. Results Abdominal adhesions were markedly reduced by emodin treatment. Compared with the control group, collagen deposition was reduced and the peritoneal mesothelial completeness rate was higher in the emodin-treated groups. Emodin had anti-inflammatory effects, reduced oxidative stress, and promoted the movement of the intestinal tract (P < 0.05). Conclusion Emodin significantly reduced intra-abdominal adhesion formation in a rat model.