Pyrrolidine dithiocarbamate, a inhibitor of NF-κB, enhances chemosensitivity of ovarian cancer cells to cisplatin

doi:10.3872/j.issn.1007-385X.2008.4.012

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Archive > Volume 15 Issue 4 > 2008,15(4):356-360. DOI:10.3872/j.issn.1007-385X.2008.4.012 Prev Next

Pyrrolidine dithiocarbamate, a inhibitor of NF-κB, enhances chemosensitivity of ovarian cancer cells to cisplatin

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Abstract:

Abstract Objective: To determine the promoting effect of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NFκB, on the sensitivity of human ovarian cancer cell line SKOV3 to chemoagent cisplatin and the possible mechanisms. Methods:SKOV3 cells were treated with various concentrations of cisplatin and PDTC combination for different periods. Then the growth inhibition of SKOV3 cells were observed by MTT assay, expression of IκBα and P65 protein by Western blotting assay, and apoptosis of cells by flow cytometry. Results: Separate application of both cisplatin（0.1-10 μg/ml）and PDTC（10-40 μmol/L L）significantly inhibited the growth of SKOV3 cells and caused cell apoptosis(P<0.05 orP<0.01). Even at lower concentration, cisplatin（0.01 μg/ml）combined with PDTC （2.5, 5 μmol/L）resulted more significant growth inhibition and apoptosis of SKOV3 cells than cisplatin alone (both P<0.05). Cisplatin alone reduced cytoplasmic IκBα protein in the cytoplasm and increased nuclear P65 protein compared with control group(both P<0.05), which could be reversed by addition of PDTC. Conclusion: Low dose of PDTC can enhance the chemosensitivity of ovarian cancer cells to cisplatin, which might be related to PDTCinduced IκBα protein and the subsequent inhibition of nuclear translocation of P65 protein.

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Surpported by the National Natural Science Foudation of China (No.30271316)

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