Search

Aflatoxin B1 (AFB1), a kind of mycotoxin, exerts its cytotoxicity by increasing the oxidative damage of target organs, especially the liver. In vivo and in vitro experiments were carried out to elu...

Background The progression of hepatocellular carcinoma (HCC) involves multi-factor, multi-step interactions. It has been reported that the high expression of interleukin-6 receptor (IL-6R) plays an important role in the occurrence and development of tumors, but the regulation mechamismof IL-6R expression and its function in HCC have not been adequately reported. Methods Western Blot was used to evaluate the phosphorylation of key kinases in JAK2/STAT3 pathway and the protein expression levels of related proliferative molecules, migration molecules and apoptotic molecules. The anti-apoptosis, migration and proliferation abilities of cells of each group were analyzed using JC-1 measures cell apoptosis, EdU method to detect cell apoptosis, clone formation experiment and Transwell. Result The expression of IL-6R in HCC cells (HepG2, Huh7 and SK-Hep1) was higher than that in normal hepatocytes (THLE-2 and THLE-5), and the protein expression of IL-6R was relatively highest in SK-Hep1 and relatively lowest in HepG2. Compared with the HepG2IL − 6 cell line, the protein levels of apoptotic molecules c-Caspase7 and c-Caspase3 were lower, while the protein levels of proliferative molecules p-P70S6K and migration molecules MMP9 and MMP2 were higher, showing stronger anti-apoptosis, proliferation and migration abilities. Compared with SK-Hep1 in SK-Hep1TCZ and SK-Hep1IL − 6R−, the protein levels of apoptotic molecules c-Caspase7 and c-Caspase3 were higher, while the protein levels of proliferative molecules p-P70S6K and migration molecules MMP9 and MMP2 were lower. It showed strong apoptotic ability and low proliferation and migration ability. Interestingly, IL-6 up-regulated the expression of IL-6R by activating JAK2/STAT3 signaling pathway. The expression of IL-6R protein was also down-regulated after lentivirus knockdown of STAT3. In subcutaneous tumor-bearing experiments in nude mice, compared with SK-Hep1 group, the up-regulation of IL-6R expression after JAK2/STAT3 signaling pathway activation by IL-6 in SK-Hep1IL − 6 group significantly improved the tumor growth ability. However, the expression of IL-6R protein was down-regulated and the terminal tumor volume was significantly down-regulated in the lentiviral STAT3 knockdown group, which inhibited the tumor growth ability. Conclusions The results showed that IL-6 regulated the transcription of IL-6R through the activation of JAK2/STAT3 signaling pathway, thereby promoting the progression of HCC. The result are expected to provide experimental basis for IL-6R as a potential therapeutic target for HCC.

Epithelial mesenchymal transition (EMT) and inflammation have been identified as carcinogenic agents. This study aims to investigate whether inhibition of trichloroethylene (TCE) associated hepatocellular carcinoma (HCC) by curcumin is associated with inflammation and EMT.In the current study, TCE sub-chronic cell model was inducedTCE induces hepatocyte migration, colony formation, and EMTCurcumin has anti-inflammatory and anti-proliferative effects, and inhibits the development of HCC induced by TCE by reversing IL-6/STAT3 mediated EMT.

Multidrug resistance is the main obstacle to curing hepatocellular carcinoma (HCC). Acid-sensing ion channel 1a (ASIC1a) has critical roles in all stages of cancer progression, especially invasion and metastasis, and in resistance to therapy. Epithelial to mesenchymal transition (EMT) transforms epithelial cells into mesenchymal cells after being stimulated by extracellular factors and is closely related to tumour infiltration and resistance. We used Western blotting, immunofluorescence, qRT-PCR, immunohistochemical staining, MTT, colony formation and scratch healing assay to determine ASIC1a levels and its relationship to cell proliferation, migration and invasion. ASIC1a is overexpressed in HCC tissues, and the amount increased in resistant HCC cells. EMT occurred more frequently in drug-resistant cells than in parental cells. Inactivation of ASIC1a inhibited cell migration and invasion and increased the chemosensitivity of cells through EMT. Overexpression of ASIC1a upregulated EMT and increased the cells' proliferation, migration and invasion and induced drug resistance; knocking down ASIC1a with shRNA had the opposite effects. ASIC1a increased cell migration and invasion through EMT by regulating α and β-catenin, vimentin and fibronectin expression via the AKT/GSK-3β/Snail pathway driven by TGFβ/Smad signals. ASIC1a mediates drug resistance of HCC through EMT via the AKT/GSK-3β/Snail pathway.

Background: The main obstacle to the cure of hepatocellular carcinoma (HCC) is multidrug resistance. Acid sensing ion channel 1a (ASIC1a) acts as a critical roles in all stages of cancer progression, especially invasion and metastasis as well as in resistance to therapy. Epithelial to mesenchymal transition (EMT) is a phenomenon in which epithelial cells transform into mesenchymal cells after being stimulated by extracellular factors and is closely related to tumor infiltration and resistance. Methods: Western blotting assay, Immunofluorescence (IF) staining, Immunohistochemistry (IHC) staining, MTT and colony formation assay and scratch healing assay were used to detect the level of ASIC1a and the cell proliferation, migration and invasion capabilities in this research.Results: In this research, we found that the protein of ASIC1a is overexpressed in HCC cancer tissues. In addition, we identified that the levels of ASIC1a are highly expressed in resistant HCC cells. Compared with the parental cells, EMT occurred more frequently in drug-resistant cells. Functional studies demonstrated that inactivation of ASIC1a restrained cell migration and invasion and enhanced the chemosensitivity of cells through EMT. In HCC cells, the overexpression of ASIC1a stimulates the up-regulation of EMT characterization molecular level and proliferation, migration and invasion capabilities and further induces drug resistance, while knocking down ASIC1a with short hairpin RNA (shRNA) has the opposite effect. Further investigations found that ASIC1a increased cell migration and invasion through EMT by regulating α and β-catenin, vimentin and fibronectin expression via AKT/GSK-3β/Snail pathway. Conclusions: Our study demonstrated that ASIC1a acts an important assignment in drug resistance of HCC through EMT via AKT/GSK-3β/Snail pathway, thereby lending a latent therapeutic objective and new ideas regarding to HCC.