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AIM: To explore the potential mechanism of action of Pingxiao capsule in the treatment of breast cancer. METHODS: TCMSP, TCM-ID, GeneCards and other databases were used to screen the related targets of Pingxiao capsule and breast can-
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AIM: To investigate the ability of quercetin to reverse acquire adriamycin (ADR) resistance and explored its probably mechanism. METHODS: The CCK-8 assay was used to detect the cytotoxicity of quercetin in MCF-7/ADR cells and the reversal effect of ADR. The colony formation assay and Hoechst 332582 staining were used to detect the cell proliferation, cell apoptosis and the accumulation of rhodamine 123 (Rh123) respectively. The RNA expression levels of GAS5 and ABCB1 were detected by qRT-PCR. The protein expression levels of GSK-3β, β-catenin, c-MYC, cyclin D1, and ABCB1 were detected by Western blot. RESULTS: Quercetin (10, 20, 40 μmol/L) significantly enhanced the sensitivity of MCF-7/ADR to ADR, inhibitd cell proliferation, and increased the intracellular accumulation of Rh123. Treatment with quercetin in MCF-7/ADR cells, the expression levels of GAS5 and GSK-3β were increased, whereas the expression levels of β-catenin, c-myc, cyclin D1 and ABCB1 were decreased. Further research revealed that reduction of GAS5 by RNA interference (si-GAS5) induced inhibitory effects on the expressions of GAS5 and GSK-3β, and enhanced the expressions of β-catenin, c-myc, cyclin D1, and ABCB1. Furthermore, treatment by quercetin combined with si-GAS5 in MCF-7/ADR cells, the expressions of these proteins were effectively reversed in comparison to quercetin combined with siRNA negative control (sncRNA). CONCLUSION: Quercetin increases the expression of GAS5by GSK-3β/β-catenin signaling pathway, which inhibits the expression of ABCB1, ultimately reversing ADR resistance in the MCF-7/ADR cells.
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BACKGROUND: A large number of experiments in vivo and in vitro have shown that mesenchymal stem cells may obviously inhibit the lymphocytes and other immunocytes.OBJECTIVE: To investigate the effect of human umbilical cord mesenchymal stem cell transplantation on the immune function and prognosis of patients suffering decompensated liver cirrhosisn due to hepatitis B.METHODS: 118 patients with decompensated cirrhosis due to hepatitis B were randomly divided into control group (n=59) and observation group (n=59). The two groups all received normal medical treatment, and in addition, the observation group also received human umbilical cord mesenchymal stem cell transplantation. (4.0-4.5)×108 stem cells were transplanted twice by intervention via proper hepatic artery (10 mL) and intravenous infusion (10 mL) within 1 week after admission. The levels of serum interleukin-6, tumor necrosis factor-α, interleukin-10, transforming growth factor-β and the percentage of lymphocyte subsets in the peripheral blood were determined in the two groups before and 1, 4 weeks after treatment. The model for end-stage liver disease (MELD) score and Child-Pugh score of 118 patients after treatment for 12 weeks were observed and recorded, and liver failure, complications and survival during follow-up period in the two groups were observed. RESULTS AND CONCLUSION: After treatment for 1 and 4 weeks, the levels of serum interleukin-6 and tumor necrosis factor-α in the observation group were significantly lower than those in the control group (P < 0.05 or P <0.001), but the levels of serum interleukin-10 and transforming growth factor-β in the observation group were significantly higher than those in the control group (P < 0.05 or P < 0.001). After treatment for 1 week, the percentagesof CD3+CD4+T cell and CD4+CD25+Treg cells in the observation group were significantly higher than those in the control group (P < 0.001), but the percentages of CD3+CD8+ T cells and CD3-CD19+ B cells were significantly lower than those in the control group (P < 0.05 or P < 0.001). After treatment for 4 weeks, the percentages of CD3+ T cell ,CD3+CD4+ T cells and CD4+CD25+ Treg cells in the observation group were significantly higher than those in the control group (P < 0.05 or P < 0.001), but the percentages of CD3+CD8+ T cell and CD3-CD19+ B cells were significantly lower than those in the control group (P < 0.05 or P < 0.001). After treatment for 12 weeks, the MELD and Child-Pugh scores in the observation group were significantly lower than those in the control group (P < 0.05).During the follow-up period, none of the cases in the observation group developed liver failure, but five cases in the control group did. In addition, the incidence of complications and cumulative mortality in the observation group were significantly lower than those in the control group (P < 0.05). These results show that the human umbilical cord mesenchymal stem cell transplantation may alleviate liver inflammation and improve liver function, and then may reduce the incidence of hepatic failure and mortality for patients with decompensated cirrhosis due to hepatitis B.
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Aim To study the mechanism of 8-isopro-pylaminomethyl hesperitin ( IPHP ) intestinal absorp-tion using Caco-2 cell lines. Methods Using Caco-2 cell lines as an intestinal epithelial cell model, the effects of drug concentration, temperature, pH, P-gly-coprotein ( P-gp) inhibitor verapamil and multidrug re-sistance protein 2 ( MRP2 ) inhibitors MK-571 or pro-benecid on IPHP transport across Caco-2 cell lines were all investigated. Results The transportation of IPHP was related to drug concentration. The Papp ( AP-BL) ( × 10 -5) was (2. 21 ± 0. 200) cm·s-1,(3. 56 ± 0. 306) cm·s-1,(3. 81 ± 0. 179) cm·s-1,(4. 23 ± 0. 229 ) cm · s-1 , ( 4. 17 ± 0. 262 ) cm · s-1 , re-spectively, and Papp(BL-AP) ( × 10 -5) was (3. 57 ±0. 209) cm·s-1,(4. 51 ± 0. 113) cm·s-1,(4. 97 ± 0. 229) cm·s-1,(5. 24 ± 0. 550) cm·s-1,(5. 07 ± 0. 557) cm·s-1,respectively. Efflux rate was 1. 61, 1. 26,1. 3,1. 23,1. 21,respectively. Temperature and pH both influenced the transport, While the P-gp in-hibitor verapamil had no effect on the transport of IPHP. MRP2 inhibitors MK-571 or probenecid led to an apparent decrease in the efflux of IPHP. Conclu-sion The results suggest that the transport of IPHP is mainly passive diffusion, and MRP2 but not P-gp may be involved in the transport of IPHP.
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Aim To observe the effect of melittin on human hepatocelluar carcinoma HepG2 cell prolifera-tion in vitro and its further mechanisms.Methods The capacity of cellular proliferation and apoptosis was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,Hoechst 33258 assay and Annexin V-FITC /PI assay.The mR-NA expression of Shh, PTCH1, SMO, GLi1 and HDAC2 was performed by qRT-PCR.And the protein expression of Shh,PTCH1,SMO,GLi1 and HDAC2 was assessed by western blotting.Results Our study found that melittin effectively inhibited cell prolifera-tion and promoted cell apoptosis in vitro using MTT method and Flow cytometry.The mRNA and protein expression of Shh,PTCH1,SMO,GLi1 and HDAC2 were obviously decreased after treated with various con-centrations of melittin for 48h in HepG2 cells.Conclu-sions Taken together,our data suggest that melittin could inhibit cell proliferation and promote cell apopto-sis,reduce the level of HDAC2 and down-regulate the Hedgehog signaling pathway in this process simultane-ously.
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Aim To study the transport of geniposide and geniposide in Zhizi Bopi Decoction in MDCK cell membrane model. Methods The safety concentration of geniposide and Zhizi Bopi Decoction in MDCK cells were determined by MTT assay. Then the MDCK cell membrane model was used to investigate the transport of drugs. Firstly, the effects of time, drug concentra-tion, P-gp inhibitor and EDTA on the absorption and transport of geniposide were studied systematically. Secondly, the differences were compared between the transport of the same concentration of geniposide as single compound and that in Zhizi Bopi Decoction in MDCK cell model. The drug concentration was deter-mined by high performance liquid chromatography ( HPLC) to calculate the apparent permeability coeffi-cient (Papp). Results Geniposide transport in MDCK cell monolayer was time and concentration dependent. P-gp inhibitors had no significant effect on its transport and the transport of geniposide was enhanced by ED-TA. The absorption Papp of different concentrations of geniposide in Zhizi Bopi Decoction were ( 8. 96 ± 0. 35 ) × 10 -7 cm · s-1 , ( 8. 95 ± 0. 38 ) × 10 -7 cm · s-1 and (9. 16 ± 0. 30) × 10 -7 cm·s-1, significantly higher than the absorption Papp of geniposide as single compound(5. 85 ± 0. 44) × 10 -7 cm·s-1, (6. 88 ± 0. 38) × 10 -7 cm·s-1 and (6. 31 ± 0. 19) × 10 -7 cm ·s-1 ( P<0. 05 ) . Conclusion The transport of ge-niposide in MDCK cell membrane model is passive transport and is not affected by P-gp. Geniposide may transport via the paracellular route. The Zhizi Bopi De-coction can increase the absorption of geniposide.