Fig. 6.

Inhibition of miR-21 and WIP1 sensitizes HER2+ breast cancer cells to the treatment of trastuzumab. a, b Parental or trastuzumab-resistant HER2+ breast cancer cells (HER18 or BT-474) were incubated with trastuzumab at the indicated concentrations for 72 h. The cell viability was then measured and these results are presented as % vehicle ± SD. The cell lysates were subjected to western blot analyses with the indicated antibodies (right panels). c, d HER18R (c) or BT-474R (d) cells with or without Dox-induced miR-21 knockdown were incubated with indicated concentrations of GSK2830371 for 72 h. The cell viability was then measured and these results are presented as % vehicle ± SD. The cell lysates were subjected to western blot analyses with the indicated antibodies (right panels). e HER18R cells with or without Dox-induced miR-21 knockdown were incubated with GSK2830371 (0.2 µM) and/or trastuzumab (1 µg ml⁻¹) for 72 h. The cell viability was then measured and these results are presented as % vehicle ± SD. f, g Gross tumor images (f) and tumor growth curves (g) of xenograft tumors derived from orthotopically implanted parental or trastuzumab-resistant HER18 cells expressing Dox-inducible WIP1 or DDX5 shRNA or anti-miR21 oligonucleotides with trastuzumab treatment (5 mg kg⁻¹, twice per week). *p < 0.05; **p < 0.01; ***p < 0.001; unpaired 2-tailed t-test (c–e) and one-way ANOVA followed by Tukey’s t test (g) were used. Data are presented as mean ± SD and are representative of 3 independent experiments in a–e