Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice

BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown. MATERIALS/METHODS: In the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU (10 mg.kg-1.d-1, i.p), or AHCC (360 mg.kg-1.d-1, i.g) plus 5-FU, respectively, for 5 d. CD3+, CD4+, CD8+, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and TNFalpha in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS: Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of CD3+, CD4+, and NK cells (P < 0.01), and ratio of CD4+/CD8+ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and TNFalpha compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS: These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.

Combination of wogonin with 5-fluorouracil exhibits antagonistic effect on human Hep-G2 hepatocellular carcinoma cells / 药学实践杂志

Objective To investigate the antagonistic effect of wogonin in combination with 5-fluorouracil (5-FU) on the proliferation of human Hep-G2 hepatocellular carcinoma cells .Methods Human hepatocellular Hep-G2 cells were divided into experimental group (wogonin group ,5-FU group ,wogonin + 5-FU group) and control group .MTT method was used to eval-uate tumor cell proliferation in vitro ,flow cytometry analysis was used to evaluate tumor cell apoptosis .Results The results showed that the wogonin inhibited the proliferation of tumor cells at the concentrations of 5 ,10 ,20 and 40 μmol/L after 24 h and 48 h treatment respectively (P<0.05);5-FU also inhibited the proliferation of tumor cells at the concentrations of 5 ,10 , 20 and 40 mg/L after 24 h and 48 h treatment respectively (P< 0.05) .However when wogonin was combined with 5-FU (wogonin+5-FU group) ,an antagonistic effect was observed on tumor cell proliferation (P<0.05) .When cells were treated by wogonin+5-FU for 48 h ,the combined index (CI) value slowed a dose-dependent antagonistic effect (P<0.05) .Conclusion Wogonin has anti-tumor effect .However when wogonin was combined with 5-FU ,an obvious antagonistic effect on 5-FU′s anti-tumor action was observed .The underlying mechanism deserves further study .

Role of the IGF/HGF/Gln on the culture of the intestinal organoid in vitro / 肠外与肠内营养

Objective: To investigate the nutritious effects of IGF, HGF and Gln on intestinal mucosal precursor cells in vitro.Methods: Different combinations of IGF,HGF and Gln were used to observe their effects on the expansion and development of the cultured intestinal mucosal precursor cells.Results: The combination of IGF,HGF and Gln could markedly promote the expansion of cultured intestinal mucosal precursor cells.Although IGF or HGF alone could promote the expansion of intestinal mucosal precursor cells, they had little effects on the development.On the contrary,Gln alone can promote the development of intestinal mucosal precursor cells,but it had little effects on their expansion.Conclusion: IGF,HGF or Gln alone has little effects on the expansion and development of the intestinal mucosal precursor cells.When they are used together,they can efficiently provide the essential stimuli for the expansion of the cultured intestinal mucosal precursor cells in vitro and enable the recombination of the different cells and formation of intestinal mucosa-like structure in vitro.

Dexamethasone enhances aorta-derived CD_(105)~+ mesenchymal stem cells to differentiate into adipocytes / 中国病理生理杂志

AIM: To investigate whether aorta-derived CD_(105)~+ cells show characteristics of mesenchymal stem cells, and if dexamethason enhances this kind of CD_(105)~+ cells to differentiate into adipocytes. METHODS: The distribution of CD105 in aorta was assessed by immunohistochemistry. The aorta wall cells were isolated and immunophenotypes were identified by FACS. CD_(105)~+ cells were sorted using MACS CD105 micromagnetic beads. The differentiation of CD_(105)~+ cells into adipocytes and osteoblasts was induced under different conditions and indicated by staining of Oil red O, detecting of alkaline phosphatase activity, calcium accumulation stained with silver nitrate and transmission electron microscope analysis, respectively. RESULTS: The endothelial cells, a part of medial smooth muscle cells and adventital fibroblasts were CD105 positive. The isolated aortic arch cells were positive for CD105, CD106, CD44, CD29, and negative for CD45, CD11a, CD11b and HLADR. The CD_(105)~+ cells differentiated into adipocytes contained Oil-Red-O-positive lipid droplets, the osteocytes with calcium deposition and alkaline phosphatase activity. Ultrastructurally, it was observed that some needle-shaped crystal calcium deposition similar to bone spicules was inside the cytoplasm of induced osteocytes. When the dexamethason was absent in the adipogenic medium, there were no adipocytes with lipid droplets. CONCLUSION: The results demonstrate that CD_(105)~+ cells show characters of MSCs reside in aortic wall, and is able to differentiate into adipocytes and osteocytes in vitro. Dexamethasone enhances aorta-derived CD_(105)~+ with characters of MSCs to differentiate into adipocytes. These suggeste that MSCs might be related with atherosclerosis. [

Effects of CI-930 on Vascular Resistance and Rat Aortic Strip Contraction / 第二军医大学学报

The effects of C1-930, a known selective phosphodiesterase 111 inhibitor, on vascular resistance and rat aortic strip contraction were studied CI-930 025mg/kg injected into the perfused artery, reduced vascular resistance markedly in femoral artery and internal carotid artery in anaesthetized rats. The action lasted for about 15-20 min. CI-930 in vitro inhibited norepinephrine (NE) and TXA2/PGH, mimetic U-46619 induced rat aortic strip contraction significantly with PD, values of 6.71 and 5.5 respectively. The inhibitory effects of CI-930 on NE and U-46619 induced contraction were more potent than that of KG induced contraction. CI-930 0.01 - 10?mol/L exhibited a potential inhibitory effects on intracellular Ca2+ dependent contraction of rat aortic strip induced by NE, but had no effect on extracellular Ca2+ dependent contraction. The results suggest that CI-930 can possess a potent intracellular Ca2+ dependent vasodilating effects in vitro and in vivo.