Figure 5.
Vactosertib suppresses ROS stress generated by radiotherapy. (A) Protein and mRNA expression of NOX4 in breast cancer cell lines (4T1-Luc and MDA-MB-231). Protein expression of NOX4 in 4T1-Luc and MDA-MB-231 cells were analyzed by western blot analysis. Protein expression was normalized by that of GAPDH. The mRNA expression level of Nox4 in 4T1-Luc cells was analyzed by quantitative reverse transcription¬–polymerase chain reaction. The mRNA expression level of Nox4 was normalized by that of Ppia mRNA. (B) Protein expression of 4HNE in 4T1-Luc and MDA-MB-231 cells was determined by western blot analysis. Protein expression was normalized by that of GAPDH. Data represent means of three independent experiments performed in triplicate. Significance evaluation was performed by one-way analysis of variance (ANOVA) with Bonferroni post-hoc test (*, **, and *** indicate p < 0.05, p < 0.01, and p < 0.005, respectively). (C) Summary plot of radiation-induced epithelial-to-mesenchymal transition (EMT), breast cancer stem cells, and ROS stress generation mediated by TGF-β signaling. TGF-β-induced EMT and CSC properties promote metastasis to distant organs and cancer recurrence. An ALK5 inhibitor, vactosertib, suppresses TGF-β-induced EMT, CSC properties, and ROS stress generation. Vactosertib may be an attractive strategy for prevention of cancer metastasis and recurrence in breast cancer patients undergoing radiotherapy.