Husseinjacobs2931

Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy worldwide with poor prognosis and high metastasis and recurrence rates. Although apatinib has been demonstrated to have potential antitumor activity in multiple solid tumors, the underlying mechanism of apatinib in HCC treatment remains to be elucidated. In the present study, apatinib were used to treat HCC cells transfected with or without VEGFR2 overexpression vectors. The proliferation of HCC cells was detected by MTT assay. The migration and invasion of HCC cells were detected by wound healing assay and Transwell assay. The ability of angiogenesis of HCC cells were detected by tube formation assay. The related protein expression levels were detected by western blotting. The present study aims to investigate the effect and potential mechanism of apatinib on the migration, invasion and angiogenesis of HCC cells. It was found that apatinib treatment significantly inhibited the proliferation, migration and invasion of Hep3b cells and suppressed angiogenesis in HUVECs. In addition, apatinib inhibited the epithelial‑mesenchymal transition of Hep3b cells by increasing the expression of the epithelial hallmarks E‑cadherin and α‑catenin and decreased the expression of the mesenchymal hallmarks N‑cadherin and vimentin. These effects were associated with the downregulation of VEGF and VEGFR2 and suppression of the PI3K/AKT signaling pathway. Thus, apatinib inhibited cell migration, invasion and angiogenesis by blocking the VEGF and PI3K/AKT pathways, supporting an effective therapeutic strategy in the treatment of HCC.O‑GlcNAcylation is a dynamic and reversible post‑translational modification of proteins that is modulated by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA). Alterations in the protein expression of O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) can be induced by multiple factors. However, little is known of the effects of chemotherapeutic agents on O‑GlcNAcylation and the relevant molecular mechanisms in cancer cells. In the present study, to investigate whether cisplatin alters protein O‑GlcNAcylation and to explore whether protein O‑GlcNAc modification affects the antitumor activity of cisplatin, experiments were performed in vitro and in vivo. The results indicated that cisplatin treatment resulted in an enhancement of global protein O‑GlcNAc levels in the H1299, Hep G2 and MCF‑7 cells in vitro and in vivo. Cisplatin upregulated the protein and mRNA expression levels of OGT and OGA in H1299 cells. Moreover, cisplatin induced the significant enhancement of the enzymatic activity of OGT in H1299 cells. On the contrary, the activation of OGA decreased in response to cisplatin exposure in H1299 cells. Cisplatin inhibited the activity of AMP‑activated protein kinase (AMPK) by decreasing the AMP/ATP ratio. The present study also revealed that the decreased AMPK activation inhibited glutamine‑fructose‑6‑phosphate aminotransferase (isomerizing) 1 (GFAT1) phosphorylation and subsequently promoted the activity of GFAT1. Cisplatin‑induced GFAT1 activation elevated the production of the donor substrate, uridine 5‑diphospho‑N‑acetylglucosamine (UDP‑GlcNAc). However, alterations in the O‑GlcNAc levels by the inhibition of OGT and OGA did not affect the sensitivity of lung cancer cells to cisplatin. On the whole, the present study demonstrates that cisplatin enhances protein O‑GlcNAcylation by altering the activity of OGT, OGA and AMPK in vitro and in vivo.Prostate cancer is a main health risk for males with a high incidence and mortality. selleck The present study aimed to examine the effects of long non‑coding RNA (lncRNA) MIR4435‑2HG binding with ST8SIA1 on the proliferation, invasion and migration of prostate cancer cells via the activation of the FAK/AKT/β‑catenin signaling pathway. The expression of MIR4435‑2HG and ST8SIA1 in prostate cancer cell lines, and the transfection efficacy were analyzed by RT‑qPCR. The proliferation, clone formation ability, and the invasion and migration of transfected cells were detected by CCK‑8 assay, clone formation assay, Transwell assay and wound healing assay, respectively. Plasmids were injected subcutaneously into mice to construct a xenograft tumor model. The expression levels of proteins related to proliferation, apoptosis, invasion and migration, and the FAK/AKT/β‑catenin pathway were detected by western blot analysis. The results revealed that MIR4435‑2HG expression was increased in the prostate cancer cell lines and MIR4435‑2HG expression was the highest in the PC‑3 cells. Interference with MIR4435‑2HG inhibited the proliferation, clone formation ability, and the invasion and migration of PC‑3 cells, as well as tumor growth by suppressing the activation of the FAK/AKT/β‑catenin signaling pathway. MIR4435‑2HG was demonstrated to target ST8SIA1. ST8SIA1 expression was also increased in the prostate cancer cell lines and MIR4435‑2HG expression was the highest in the PC‑3 cells. Interference with ST8SIA1 inhibited the promoting effects of MIR4435‑2HG on the proliferation, invasion and migration of PC‑3 cells, as well as tumor growth by suppressing the activation of the FAK/AKT/β‑catenin signaling pathway. On the whole, the present study demonstrates that interference with MIR4435‑2HG, combined with ST8SIA1, inhibits the proliferation, invasion and migration of prostate cancer cells in vitro and in vivo by blocking the activation of the FAK/AKT/β‑catenin signaling pathway.The primary pathological changes observed in osteoarthritis (OA) involve inflammation and degeneration of chondrocytes. link2 3‑phosphoglycerate dehydrogenase (Phgdh), a rate‑limiting enzyme involved in the conversion of 3‑phosphoglycerate to serine, serves as a crucial molecular component of cell growth and metabolism. However, its effects on chondrocytes in OA have not been determined. In the present study, a rat model of OA was used to investigate the expression levels of Phgdh in vivo and in vitro. Additionally, the role of Phgdh in extracellular matrix (ECM) synthesis, inflammation, apoptosis and oxidative stress levels of chondrocytes was detected in vitro. Phgdh expression was decreased in OA, and Phgdh overexpression promoted ECM synthesis, decreased levels inflammatory cytokines, such as Il‑6, TNF‑α, a disintegrin and metalloproteinase with thrombospondin motifs 5 and MMP13, and decreased apoptosis. Furthermore, expression of Phgdh effectively increased expression levels of the cellular antioxidant enzymes catalase and superoxide dismutase 1, and decreased the levels of reactive oxygen species in chondrocytes; and this may have been regulated by a Kelch like ECH associated protein 1/nuclear factor erythroid 2‑related factor 2 axis. Taken together, these results suggest that Phgdh may be used to manage the progression of OA.Stomatin‑like protein 2 (SLP‑2) is associated with poor prognosis in several types of cancer, including pancreatic cancer (PC); however, the molecular mechanism of its involvement remains elusive. The present study aimed to elucidate the role of this protein in the development of PC. Human PC cell lines AsPC‑1 and PANC‑1 were transfected by a vector expressing SLP‑2 shRNA. Analyses of cell proliferation, migration, invasion, chemosensitivity, and glucose uptake were conducted, while a mouse xenograft model was used to evaluate the functional role of SLP‑2 in PC. Immunohistochemical analysis was retrospectively performed on human tissue samples to compare expression between the primary site (n=279) and the liver metastatic site (n=22). Furthermore, microarray analysis was conducted to identify the genes correlated with SLP‑2. In vitro analysis demonstrated that cells in which SLP‑2 was suppressed exhibited reduced cell motility and glucose uptake, while in vivo analysis revealed a marked decrease in the number of liver metastases. link3 Immunohistochemistry revealed that SLP‑2 was increased in liver metastatic sites. Microarray analysis indicated that this protein regulated the expression of glutamine‑fructose‑6‑phosphate transaminase 2 (GFPT2), a rate‑limiting enzyme of the hexosamine biosynthesis pathway. SLP‑2 contributed to the malignant character of PC by inducing liver metastasis. Cell motility and glucose uptake may be induced via the hexosamine biosynthesis pathway through the expression of GFPT2. The present study revealed a new mechanism of liver metastasis and indicated that SLP‑2 and its downstream pathway could provide novel therapeutic targets for PC.Lung cancer is the leading cause of cancer‑associated death worldwide and exhibits intrinsic and acquired therapeutic resistance to cisplatin (CIS). The present study investigated the role of mTOR signaling and other signaling pathways after metformin (MET) treatment in control and cisplatin‑resistant A549 cells, mapping pathways and possible targets involved in CIS sensitivity. MTT, flow cytometry, clonogenic assay, western blotting, proteomic analysis using the Stable Isotope Labeling by Amino acids in Cell culture (SILAC) approach and reverse transcription‑quantitative PCR were performed. The results revealed that CIS treatment induced mTOR signaling pathway overactivation, and the mTOR status was restored by MET. MET and the mTOR inhibitor rapamycin (RAPA) decreased the viability in control and resistant cells, and decreased the cell size increase induced by CIS. In control cells, MET and RAPA decreased colony formation after 72 h and decreased IC50 values, potentiating the effects of CIS. Proteomics analysis revealed important pathways regulated by MET, including transcription, RNA processing and IL‑12‑mediated signaling. In CIS‑resistant cells, MET regulated the apoptotic process, oxidative stress and G2/M transition. Annexin 4 (ANXA4) and superoxide dismutase 2 (SOD2), involved in apoptosis and oxidative stress, respectively, were chosen to validate the SILAC analysis and may represent potential therapeutic targets for lung cancer treatment. In conclusion, the chemosensitizing and antiproliferative effects of MET were associated with mTOR signaling and with potential novel targets, such as ANXA4 and SOD2, in human lung cancer cells.Spinal cord injury (SCI) is one of the most debilitating of all the traumatic conditions that afflict individuals. For a number of years, extensive studies have been conducted to clarify the molecular mechanisms of SCI. Experimental and clinical studies have indicated that two phases, primary damage and secondary damage, are involved in SCI. The initial mechanical damage is caused by local impairment of the spinal cord. In addition, the fundamental mechanisms are associated with hyperflexion, hyperextension, axial loading and rotation. By contrast, secondary injury mechanisms are led by systemic and cellular factors, which may also be initiated by the primary injury. Although significant advances in supportive care have improved clinical outcomes in recent years, a number of studies continue to explore specific pharmacological therapies to minimize SCI. The present review summarized some important pathophysiologic mechanisms that are involved in SCI and focused on several pharmacological and non‑pharmacological therapies, which have either been previously investigated or have a potential in the management of this debilitating injury in the near future.