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The dendritic cell (DC)-regulatory T (Treg) system serves a leading role in the immunosuppression of the tumor microenvironment, which is not conducive to radiotherapy and chemotherapy treatment for lung cancer. The present study aimed to investigate the effect of oxymatrine (OMT) on the DC-Treg system in the tumor microenvironment in vitro and to examine its mechanism. The expressions of CD83 antigen, T-lymphocyte activation antigen CD86, CD11 antigen-like family member C and major histocompatibility complex II in DCs were increased upon treatment with 1 mg/ml OMT, as detected by flow cytometry. Following pretreatment with OMT, the DCs mediated the forkhead box protein P3 overexpression in primitive cluster of differentiation 4+ T cells at the protein and mRNA expression levels. The expression levels of anti-inflammatory factors, including interleukin (IL)-10, tumor growth factor-β, IL-35, and pro-inflammatory cytokines, including interferon-γ, IL-12 and IL-2, in the co-culture supernatant were increased as measured by ELISA. When DCs and DC-Tregs were co-cultured with cisplatin-resistant A549 cells, the proportion of apoptosis in the co-culture groups was increased under treatment with cisplatin, which was detected by Annexin V/propidium Iodide staining and western blotting. The present results suggested that OMT may promote the maturation of DCs, mediate the differentiation of T cells into Treg cells, and reverse the resistance of tumor cells to cisplatin in vitro. It was suggested that OMT is an important adjunct to chemotherapy through the regulation of antitumor responses.

Osteoarthritis (OA) is a multifactorial disease characterized by degeneration of the articular cartilage due to genetic and epigenetic components. The pathogenesis of OA is complex and the mechanism of chondrocyte homeostatic regulation remains to be fully elucidated. Previous studies have demonstrated that microRNAs (miRNAs/miR) contribute to cartilage dysfunction. However, the functional role of miR‑98 in interleukin‑1β (IL‑1β)‑induced chondrocyte apoptosis in OA cartilage remains to be investigated. The present study aimed to identify and characterize the expression profile of miR‑98 and apoptosis‑associated proteins in healthy and OA chondrocytes, and western blot analysis and TUNEL staining were used to evaluate the role of miR‑98 in the regulation of chondrocyte apoptosis. The present study demonstrated that miR‑98 expression was increased in OA chondrocytes in response to IL‑1β stimulation, and the expression levels of apoptosis-associated proteins, including Fas cell surface death receptor, caspase‑3, caspase‑8 and B‑cell lymphoma‑2 (Bcl‑2)-associated X protein, were also increased in IL‑1β‑stimulated chondrocytes. In addition, it was revealed that upregulation of miR‑98 was accompanied by reduced expression of Bcl‑2 following exposure to IL‑1β. IL‑1β‑induced downregulation of Bcl‑2 was associated with miR‑98‑mediated translational repression. Transfection of OA chondrocytes with a miR‑98 inhibitor had an inhibitory effect on IL‑1β‑induced cell apoptosis, increased cell proliferation and upregulated Bcl‑2 expression. It is possible that miR‑98 inhibited IL‑1β‑induced chondrocyte apoptosis by modulating Bcl‑2 expression levels. The findings of the present study indicated that the effects of miR‑98 on chondrocyte apoptosis were induced by regulation of Bcl‑2 expression. In addition, the present study confirmed that miR‑98 targeted the 3'‑untranslated region of Bcl‑2. In conclusion, miRNA‑coordinated regulation of apoptosis‑associated protein expression has been identified in OA chondrocytes following IL‑1β induction.

The primary aim of the present study was to evaluate the effects of liraglutide on glucolipotoxicity-induced liver cell apoptosis and the underlying mechanisms in Zucker diabetic fatty (ZDF) rats. The results revealed that liraglutide significantly decreased the body weight, hyperglycemia and hyperlipidemia of ZDF rats relative to those of Zucker lean (ZL) rats (P

Osteoarthritis (OA) is a multifactorial disease characterized by degeneration of the articular cartilage due to genetic and epigenetic components. The pathogenesis of OA is complex and the mechanism of chondrocyte homeostatic regulation remains to be fully elucidated. Previous studies have demonstrated that microRNAs (miRNAs/miR) contribute to cartilage dysfunction. However, the functional role of miR‑98 in interleukin‑1β (IL‑1β)‑induced chondrocyte apoptosis in OA cartilage remains to be investigated. The present study aimed to identify and characterize the expression profile of miR‑98 and apoptosis‑associated proteins in healthy and OA chondrocytes, and western blot analysis and TUNEL staining were used to evaluate the role of miR‑98 in the regulation of chondrocyte apoptosis. The present study demonstrated that miR‑98 expression was increased in OA chondrocytes in response to IL‑1β stimulation, and the expression levels of apoptosis-associated proteins, including Fas cell surface death receptor, caspase‑3, caspase‑8 and B‑cell lymphoma‑2 (Bcl‑2)-associated X protein, were also increased in IL‑1β‑stimulated chondrocytes. In addition, it was revealed that upregulation of miR‑98 was accompanied by reduced expression of Bcl‑2 following exposure to IL‑1β. IL‑1β‑induced downregulation of Bcl‑2 was associated with miR‑98‑mediated translational repression. Transfection of OA chondrocytes with a miR‑98 inhibitor had an inhibitory effect on IL‑1β‑induced cell apoptosis, increased cell proliferation and upregulated Bcl‑2 expression. It is possible that miR‑98 inhibited IL‑1β‑induced chondrocyte apoptosis by modulating Bcl‑2 expression levels. The findings of the present study indicated that the effects of miR‑98 on chondrocyte apoptosis were induced by regulation of Bcl‑2 expression. In addition, the present study confirmed that miR‑98 targeted the 3'‑untranslated region of Bcl‑2. In conclusion, miRNA‑coordinated regulation of apoptosis‑associated protein expression has been identified in OA chondrocytes following IL‑1β induction.

The development of targeted tyrosine kinase inhibitors (TKIs) has succeeded in altering the course of chronic myeloid leukemia (CML). However, a number of patients have failed to respond or experienced disease relapse following TKI treatment. Proviral integration site for moloney murine leukemia virus-1 (PIM-1) is a serine/threonine kinase that participates in regulating apoptosis, cell cycle, signal transduction and transcriptional pathways, which are associated with tumor progression, and poor prognosis. SMI-4a is a selective PIM-1 kinase inhibitor that inhibits PIM-1 kinase activity in vivo and in vitro. The present study aimed to explore the mechanism underlying the antitumor effect of SMI-4a in K562 and imatinib-resistant K562 (K562/G) cell lines. It was demonstrated that SMI-4a inhibited the proliferation of K562 and K562/G cells using a WST-8 assay. The Annexin V-propidium iodide assay demonstrated that SMI-4a induced apoptosis of K562 and K562/G cells in a dose-, and time-dependent manner. Furthermore, Hoechst 33342 staining was used to verify the apoptosis rate. The clone formation assay revealed that SMI-4a significantly inhibited the colony formation capacity of K562 and K562/G cells. Western blot analysis demonstrated that SMI-4a decreased phosphorylated (p)-Ser9-glycogen synthase kinase (GSK) 3β/pGSK3β and inhibited the translocation of β-catenin. In addition, the downstream gene expression of apoptosis regulator Bax and poly(ADP-ribose) polymerase-1 was upregulated, and apoptosis regulator Bcl-2 and Myc proto-oncogene protein expression levels were downregulated. Immunofluorescence results demonstrated changes in the expression level of β-catenin in the plasma and nucleus. The results of the present study suggest that SMI-4a is an effective drug to use in combination with current chemotherapeutics for the treatment of imatinib-resistant CML.

Zoledronic acid (ZOL), a nitrogen‑containing bisphosphonate, is widely used in metastatic bone disease. Previous studies indicate that ZOL has marked anti‑leukemia activity, however, the underlying mechanism of action remains to be elucidated. The present study aimed to explore the mechanism of the anti‑leukemia effect of ZOL in leukemia cells. It was observed that ZOL inhibited the proliferation of HL‑60 and adriamycin‑resistant HL‑60 (HL‑60/A) cells using a WST‑8 assay. An Annexin V‑propidium iodide indicated that ZOL induced apoptosis of the two cell types in a dose‑ and time‑dependent manner. Hoechst 33342 staining was also used to verify the levels of apoptosis. The colony formation assay demonstrated that ZOL significantly inhibited colony formation capacity in acute myeloid leukemia (AML) cells. This was achieved by the induction of S‑phase cell cycle arrest, downregulation of B‑cell lymphoma 2 (Bcl‑2) and upregulation of Bcl‑2 associated X protein and cleaved poly (ADP‑ribose) polymerase. The results indicate that ZOL inhibited cell proliferation by inducing apoptosis via the mitochondrial apoptotic pathway and this anti‑leukemic activity appeared notably enhanced in HL‑60/A cells. As ZOL is already available for clinical use, these results indicate that it may be an effective addition to the chemotherapeutic strategies for AML.