Figure 6.

Verteporfin-mediated regulation of the YAP1/TEAD signaling pathway restores sensitivity to antitumor activity of trastuzumab in BT-474.r2T cell line. (A) For in vitro experiments, 2.5 × 10⁶ BT-474.r2T cells were seeded in 6-multiwell plates, and treatments were initiated after 96 h. For cell proliferation assays, BT-474.r2T cells left untreated (DMSO control), treated with 15 µg/mL trastuzumab, with 50 nM verteporfin, or with a combination of trastuzumab and verteporfin for 7 days. (B) WB of YAP1, pYAP1, TEAD1, and TEAD2 proteins were extracted after 48 h of 5 µM verteporfin treatment. Data are representative out of at least three independent replicates. (C) For the mRNA expression analyses of AREG, CTGF, CYR61, and VEGFA, cells were left untreated (DMSO control) or treated with 5 µM verteporfin for 2 h. (D) Combination of trastuzumab and verteporfin decreases tumor proliferation and enhances apoptosis in mouse BT-474.r2T xenografts resistant to trastuzumab. Tumor growth and statistical analysis of control (10 mg/kg IgG ĸ), 10 mg/kg trastuzumab, 40 mg/kg with verteporfin, and combined trastuzumab with verteporfin groups of treatment.