Figure 6.

Drug efficacy can be modulated by targeting reactive oxygen species (ROS) metabolism. (A) The drug efficacies of bortezomib and docetaxel were assessed by adding a low concentration of H₂O₂ together as assessed by cell proliferation assay. The antitumor efficacy of these two drugs was diminished by exogenous ROS. Error bars indicate the mean ± SD; ns = no significance, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. (B) The drug efficacies of methotrexate and vorinostat were increased by adding a high concentration of H₂O₂ together as assessed by cell proliferation assay. Error bar indicate the mean ± SD; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. (C) The tumor inhibitory effects of bortezomib were abolished by exogenous low H₂O₂ concentrations in a U87 subcutaneous xenograft model; *p < 0.05. Error bars indicate the mean ± SEM. (D) Immuno-histochemical staining for Ki67 shows that the proliferative inhibition of bortezomib was rescued by exogenous low H₂O₂ concentrations. (E) The NF-κB inhibitory effects of bortezomib were rescued by H₂O₂ in U87 and LN229 cell lines. (F) Half-dosage of bortezomib could be sensitized by NAC in U87 cell lines; ***p < 0.001. (G) Half-dosage of bortezomib together with NAC could inhibit NF-κB pathway in U87 and LN229 cell lines.