The Effect Of Combination Of Pyrrolidine Dithiocarbamate With Docetaxel On Gastric Cancer Cells

Objective: To investigate the effect of docetaxel on nuclear factor-κB activation in humangastric cancer line SGC-7901 after docetaxel stimulation, and to observe the effect of NF-κBinhibition by Pyrrolidine-dithiocarbamate (PDTC) on docetaxel-induced apoptosis of SGC-7901.Methods: SGC-7901 cells were stimulated by different concentrations of docetaxel、PDTC orPDTC combined with Docetaxel in different groups.The Proliferation inhibitions of SGC-7901were evaluated by MTT assay.Flow cytometry was used to analyze the apoptosis rate.Thecellular distribution and expressions of nuclear factor-κappaBp65 protein were detected usingimmunocytochemistry staining.Results:1. MTT assay showed that PDTC and docetaxel significantly inhibited the proliferation ofSGC-7901 cells in a dose-dependent fashion (P<0.05).Low dose of PDTC combined withdocetaxel significantly inhibited the proliferation of SGC-7901 cells (P<0.05).2. FCM showed that the apoptotic rate of SGC-7901 cells was significantly higher in thedrug treatment groups compared with the control group and was significantly higher incombination treatment group than single Docetaxel group (P<0.05).3. Immunohistochemistry showed that NF-κBp65 was located in the cytoplasm and nucleusof SGC-7901 cells in control group. The expression of NF-κBp65 in the nucleus was increasedapparently at 24h after docetaxel induction. However, when SGC-7901 cells were previouslycultured with PDTC for 1 hour and then stimulated by docetaxel, the expression of NF-κBp65 inthe nucleus was significantly attenuated.Conclusions: Docetaxel could induce apoptosis and also trigger activation of NF-κBp65 inSGC-7901 cells.Low dose of PDTC combined with Docetaxel more significantly increased thegrowth inhibition rate and apoptosis ratio of SGC-7901 cells than single Docetaxeltreatment.Therefor, PDTC can increased the chemosensitivity of gastric cancer cells toDocetaxel.