PHF8 promotes resistance to anti-HER2 therapies in breast cancer cells through IL-6.a and b. RT-qPCR analysis of IL-6 expression. RPL13A mRNA served as the control. c and d. Human Cytokine Antibody Array blots probed with the media from the indicated cells. Western blotting was performed in duplicate, an ELISA was used to measure expression, and the regulated cytokines are marked. e. An ELISA was used to measure IL-6 secreted from HCC1954 cells with or without PHF8 knockdown; * p ≤ 0.05, ** p ≤ 0.01. f. MTT analysis of the viability of HCC1954 cells with or without PHF8 knockdown in the presence or absence of IL-6. Cells were treated doxycycline for 72 h and then reseeded into the wells of 96-well plates. IL-6 (100 ng/mL) was added to the cells 24 h before the addition of T-DM1 (48 h) (n = 5). g. Western blotting analysis of the levels of HER2, PHF8, PARP/c-PARP (cleaved PARP), and STAT3/PSTAT3 in HCC1954 cells treated as in f, γ-Tubulin served as the loading control. The data represents three independent experiments.