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  • Title: Multidrug resistance reversal in human gastric carcinoma cells by neferine.
    Author: Cao JG, Tang XQ, Shi SH.
    Journal: World J Gastroenterol; 2004 Oct 15; 10(20):3062-4. PubMed ID: 15378795.
    Abstract:
    AIM: To investigate the reversal effect of neferine on multidrug resistance in human gastric carcinoma cell line. METHODS: Cells of a human gastric cancer cells line, SGC7901, and its vincristine (VCR) -resistant variant, SGC7901/VCR, were cultivated with or without neferine and/or VCR. The cytotoxic effect of VCR was evaluated by the MTT assay. Cell apoptosis induced by VCR was determined by flow cytometry (FCM). The expression of P-glycoprotein (P-gp) and a multidrug-resistance-associated protein (MRP) in cells was examined by immunofluorescence and FCM. RESULTS: Neferine at the concentration from 2.5 micromol/L to 10 micromol/L had no cytotoxicity to SGC7901 cells, and its variant SGC7901/VCR cells. The IC50 of VCR against SGC7901 and SGC7901/VCR cells was 0.059 microg/mL and 2.32 microg/mL, respectively, indicating that SGC7901/VCR cells were 39 times more resistant to VCR than its parent SGC7901 cells. After treatment with neferine at concentrations of 2.5, 5 and 10 micromol/L, the IC(50) of VCR to SGC7901/VCR cell line decreased to 0.340, 0.128 and 0.053 microg/mL, respectively, thus, increased the chemosensitivity by 6.8-, 18.1- and 43.8-fold, respectively. SGC7901/VCR cells were apoptosis resistant to VCR. Neferine (2.5, 5 and 10 micromol/L) promoted the VCR-induced apoptosis of SGC7901/VCR cells in a dose-dependent manner. The expressions of P-gp and MRP were strongly positive in SGC7901/VCR cells, which were significantly down-regulated after treatment with neferine (10 micromol/L) for 24 h. CONCLUSION: Neferine reverses multidrug resistance of human gastric carcinoma SGC7901/VCR cells, which may be associated with the down-regulations of P-gp and MRP expression in SGC701/VCR cells.
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