PBK attenuates paclitaxel-induced autophagic cell death by suppressing p53 in H460 non-small-cell lung cancer cells.

ABSTRACT

PDZ-binding kinase (PBK) has previously been shown to mediate chemoresistance of cancer cells to anticancer drugs. However, it remains unclear how PBK regulates paclitaxel-induced cancer cell death. Here, we demonstrate that PBK hinders paclitaxel-mediated autophagic cell death in H460 non-small-cell lung cancer cells. PBK knockdown increased apoptosis, autophagy, p53 level, and LC3 puncta upon paclitaxel treatment. Moreover, p53 expression facilitated an increase in the LC3-II/LC3-I ratio in response to paclitaxel, and PBK knockdown augmented paclitaxel-mediated p53 transcriptional activity. Meanwhile, paclitaxel induced PBK-mediated p53 nuclear export and its subsequent ubiquitination in control cells, but not in PBK knockdown cells. We conclude that PBK hampers paclitaxel-induced autophagic cell death by suppressing p53, suggesting a potential role of PBK in p53-mediated H460 cell death.