Effects of antioxidant pyrrolidine dithiocarbamate on the proliferation and apoptosis of cervical cancer HeLa cells induced by carboplatin

Objective:To investigate the effects of antioxidant pyrrolidine dithiocarbamate(PDTC) combined with or without carboplatin(CBP) on the proliferation and apoptosis of cervical cancer HeLa cells.Methods:Human cervical carcinoma HeLa cell line was cultured and treated with different concentrations of PDTC,CBP,or PDTC combined with CBP in different groups.The proliferation of HeLa cells was detected with MTT assay.Flow cytometry was used to analyze the apoptosis and cell cycle distribution.The cellular distribution and expression of nuclear factor-kappa B(NF-κB)p65 protein were detected using immunocytochemistry staining.Results:MTT assay showed that PDTC significantly inhibited the proliferation of HeLa cells in a time-dependent and dose-dependent fashion(P0.01).Low dose of PDTC(12.5 μmol/L) combined with CBP significantly inhibited the proliferation of HeLa cells(P0.01).FCM showed that the apoptotic rate of HeLa cells was significantly higher in the drug treatment group compared with the control group(P0.01) and was significantly higher in combination treatment group than single CBP group(P0.01).PDTC increased the proportion of cells in G_0/G_1 phase and decreased the proportion of cells in S phase compared with the control group(P0.01).CBP arrested cells in G_2/M phase.HeLa cells were further arrested in G_2/M phase after combination therapy.The proportion of cells in S phase was decreased compared with the control group(P0.01).Immunohistochemistry showed that NF-κBp65 was mainly located in the cytoplasm of HeLa cells in the control group.The NF-κBp65 was transferred from cytoplasm to nucleus at 24 h after CBP induction.Its activity was enhanced.PDTC inhibited the enhanced activity of NF-κBp65.Conclusion:CBP induced the activation of NF-κBp65 in HeLa cells.Low dose of PDTC(12.5μmol /L) combined with CBP more significantly increased the growth inhibition rate and apoptosis ratio of HeLa cells than single CBP treatment.PDTC increased the chemosensitivity of cervical cancer cells to CBP.