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Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR

Acta pharmacologica Sinica 2005年第8期26卷 1009-1016页

作者： Xiao-qing TANG~1, Hu BI~1, Jian-qiang FENG~2, Jian-guo CAO~3 ~1 Department of physiology, Nanhua University, Hengyang 421001, China ~2 Department of physiology, Zhongshan Medical College, Sun Yat sen University, Guangzhou 510080, China ~3 Institute of Oncology, Nanhua University, Hengyang 421001, China Department of physiology Nanhua University Hengyang China Department of physiology Zhongshan Medical College Sun Yatsen University Guangzhou China Institute of Oncology Nanhua University Hengyang China

Aim: To investigate the reversal effects of curcumin on multidrug resistance （MDR） in a resistant human gastric carcinoma cell line. Methods: The cytotoxic effect of vincristine （VCR） was evaluated by MTT assay. The cell apoptosis induced by VCR was determined by propidium iodide （pI）-stained flow cytometry （FCM） and a morphological assay using acridine orange （AO）/ethidium bromide （EB） dual staining. p-glycoprotein （p-gp） function was demonstrated by the accumulation and efflux of rhodamine 123 （Rh123） using FCM. The expression of p-gp and the activation of caspase-3 were measured by FCM using fluorescein isothiocyanate （FITC）-conjugated anti-p-gp and anti-cleaved caspase-3 antibodies, respectively. Results: Curcumin, at concentrations of 5 μmol/L, 10 μmol/L, or 20 μmol/L, had no cytotoxic effect on a parent human gastric carcinoma cell line （SGC7901） or its VCR-resistant variant cell line （SGC7901/VCR）. The VCR-IC50value of the SGC7901/VCR cells was 45 times more than that of the SGC7901ceUs and the SGC7901/VCR cells showed apoptotic resistance to VCR. SGC7901/VCR cells treated with 5 μmol/L, 10μmol/L, or 20 μmol/L curcumin decreased the IC50value of VCR and promoted VCR-mediated apoptosis in a dose-dependent manner. Curcumin （10 μmol/L） increased Rh123 accumulation and inhibited the effiux of Rh123 in SGC7901/VCR cells, but did not change the accumulation and efflux of Rh123 in SGC7901 ceils. p-gp was overexpressed in SGC7901/VCR cells, whereas it was downregulated after a 24-h treatment with curcumin （10 μmol/L）. Resistant cells treated with 1 μmol/L VCR alone showed 77% lower levels of caspase-3 activation relative to SGC7901 cells, but the activation of caspase-3 in the resistant cell line increased by 44% when cells were treated with VCR in combination with curcumin. Conclusion: Curcumin can reverse the MDR of the human gastric carcinoma SGC7901/VCR cell line. This might be associated with decreased p-gp function and expression, and the promotion of caspase-3

关键词： curcumin multidrug resistance apoptosis p-glycoprotein caspase-3

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